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    641 results match your criteria Hyperglucagonemia

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    Early Onset Diabetes - Genetic And Hormonal Analysis In Pakistani Population.
    J Ayub Med Coll Abbottabad 2016 Jul-Sep;28(3):465-470
    Department of Surgery, Allama Iqbal Medical College, Lahore, Pakistan.
    Background: Mitochondrial DNA mutation and hormonal imbalance is involved in the pathogenesis of early onset diabetes but data is lacking in Pakistani population. The study was planned to delineate the clinical presentation of early onset diabetes with possible hormonal and genetic etiological factors and aascertain the possible etiological role of insulin and glucagon in these patients either on oral hypoglycaemic or subcutaneous insulin therapy.

    Methods: Retrospective, analytical case control study with conventional sampling technique carried at Centre for Research in Experimental and Applied Medicine (CREAM) affiliated with the department of Biochemistry and Molecular Biology, Army Medical College Rawalpindi from Dec 2006 to July 2011. Read More

    Recycling of glucagon receptor to plasma membrane increases in adipocytes of obese rats by soy protein; implications for glucagon resistance.
    Mol Nutr Food Res 2017 Jun 27. Epub 2017 Jun 27.
    Departmento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
    Scope: Hyperglucagonemia contributes to hyperglycemia in type 2 diabetes (T2D). Previously, we have found that soy protein normalized fasting hyperglucagonemia in obese Zucker (fa/fa) rats, sensitizing the HSL-lipolytic signaling pathway in white adipose tissue (WAT), however the mechanism remains unknown.

    Methods And Results: Zucker (fa/fa) rats were fed casein or soy protein diet in combination with soybean or coconut oil. Read More

    Challenging Differential Diagnosis of Hypergastremia and Hyperglucagonemia with Chronic Renal Failure: Report of a Case with Multiple Endocrine Neoplasia Type 1.
    Intern Med 2017 1;56(11):1375-1381. Epub 2017 Jun 1.
    Department of Diabetes and Endocrinology, Osaka Red Cross Hospital, Japan.
    A 53-year-old woman developed end-stage renal failure during a 15-year clinical course of primary hyperparathyroidism and was referred to our hospital for evaluation of suspected multiple endocrine neoplasia type 1 (MEN1). Genetic testing revealed a novel deletion mutation at codon 467 in exon 10 of the MEN1 gene. Systemic and selective arterial calcium injection (SACI) testing revealed hyperglucagonemia and hypergastrinemia with positive gastrin responses. Read More

    Hepatic lipid accumulation: cause and consequence of dysregulated glucoregulatory hormones.
    J Endocrinol 2017 Jul 20;234(1):R1-R21. Epub 2017 Apr 20.
    School of Animal and Comparative Biomedical SciencesUniversity of Arizona, Tucson, Arizona, USA
    Fatty liver can be diet, endocrine, drug, virus or genetically induced. Independent of cause, hepatic lipid accumulation promotes systemic metabolic dysfunction. By acting as peroxisome proliferator-activated receptor (PPAR) ligands, hepatic non-esterified fatty acids upregulate expression of gluconeogenic, beta-oxidative, lipogenic and ketogenic genes, promoting hyperglycemia, hyperlipidemia and ketosis. Read More

    On the role of the gut in diabetic hyperglucagonaemia.
    Dan Med J 2017 Apr;64(4)
    Patients with type 2 diabetes are characterised not only by compromised insulin secretion and action, but also by elevated plasma concentrations of the 29-amino acid peptide hormone glucagon, which generally is thought of as a pancreas-derived hormone (produced in and secreted from alpha cells in the islet of Langerhans). In patients with diabetes, circulating glucagon concentrations are elevated in the fasting state and fail to decrease appropriately or even increase in response to ingestion of nutrients. Glucagon is known to be a potent stimulator of hepatic glucose production, and, thus, the elevated glucagon concentrations in diabetes contribute decisively to the predominating trait of patients with diabetes namely hyperglycaemia. Read More

    Increased insulin resistance and glucagon levels in mild/inactive systemic lupus patients despite normal glucose tolerance.
    Arthritis Care Res (Hoboken) 2017 Mar 20. Epub 2017 Mar 20.
    School of Medicine, University of Sao Paulo, Brazil.
    Objective: To assess insulin sensitivity in patients with systemic lupus erythematosus (SLE) in response to a meal tolerance test (MTT).

    Methods: In this cross-sectional study, 33 adult females mild/inactive SLE and 16 age- and body mass index (BMI)-matched female healthy controls (CTRL) underwent a MTT and were assessed for insulin sensitivity and beta-cell function. Skeletal muscle protein expressions of total and membrane GLUT-4 were also evaluated (SLE, n=10; CTRL, n=5); muscle biopsies were performed after MTT. Read More

    Effect of Pancreatic Hormones on pro-Atrial Natriuretic Peptide in Humans.
    EBioMedicine 2017 Mar 1;17:88-94. Epub 2017 Mar 1.
    Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark; Faculty of Health, Aarhus University, Aarhus, Denmark; Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA. Electronic address:
    Plasma concentrations of pro-Atrial natriuretic peptide, proANP, are decreased in obesity and diabetes. Decreased proANP concentrations have also been noted after meal intake, and recently, a glucose-mediated regulation of ANP gene expression was reported. Hence, we evaluated the effects of insulin, glucagon and glucose on plasma proANP in a series of observational and experimental studies. Read More

    Angptl4 does not control hyperglucagonemia or α-cell hyperplasia following glucagon receptor inhibition.
    Proc Natl Acad Sci U S A 2017 Mar 31;114(10):2747-2752. Epub 2017 Jan 31.
    Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591
    Genetic disruption or pharmacologic inhibition of glucagon signaling effectively lowers blood glucose but results in compensatory glucagon hypersecretion involving expansion of pancreatic α-cell mass. Ben-Zvi et al. recently reported that angiopoietin-like protein 4 (Angptl4) links glucagon receptor inhibition to hyperglucagonemia and α-cell proliferation [Ben-Zvi et al. Read More

    Heparanase Overexpression Induces Glucagon Resistance and Protects Animals From Chemically Induced Diabetes.
    Diabetes 2017 Jan 7;66(1):45-57. Epub 2016 Oct 7.
    Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada
    Heparanase, a protein with enzymatic and nonenzymatic properties, contributes toward disease progression and prevention. In the current study, a fortuitous observation in transgenic mice globally overexpressing heparanase (hep-tg) was the discovery of improved glucose homeostasis. We examined the mechanisms that contribute toward this improved glucose metabolism. Read More

    Effects of 13-Hour Hyperglucagonemia on Energy Expenditure and Hepatic Glucose Production in Humans.
    Diabetes 2017 Jan 7;66(1):36-44. Epub 2016 Oct 7.
    Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, FL
    Glucagon (GCG) acutely stimulates energy expenditure (EE) and hepatic glucose production (HGP) in humans, but whether these effects persist during hyperglucagonemia of longer duration is unclear. Using a prospective, randomized, single-blind, crossover study design, we therefore measured EE and rates of glucose appearance (glucose RA) during three separate infusion protocols in healthy lean males: A) 10-h overnight GCG infusion (6 ng/[kg × min]) followed by 3-h infusion of GCG, octreotide (OCT), and insulin (INS) for basal replacement; B) overnight saline (SAL) infusion followed by GCG/OCT/INS infusion; and C) overnight SAL infusion followed by SAL/OCT/INS infusion. Sleep EE, measured at 6 to 7 h of the overnight infusion, was increased 65-70 kcal/24 h in A compared with B and C. Read More

    Life in the fat lane: seasonal regulation of insulin sensitivity, food intake, and adipose biology in brown bears.
    J Comp Physiol B 2017 May 16;187(4):649-676. Epub 2016 Dec 16.
    Department of Integrative Physiology and Neuroscience, Washington State University, VBRB Room 205, MS7620, Pullman, WA, 99164, USA.
    Grizzly bears (Ursus arctos horribilis) have evolved remarkable metabolic adaptations including enormous fat accumulation during the active season followed by fasting during hibernation. However, these fluctuations in body mass do not cause the same harmful effects associated with obesity in humans. To better understand these seasonal transitions, we performed insulin and glucose tolerance tests in captive grizzly bears, characterized the annual profiles of circulating adipokines, and tested the anorectic effects of centrally administered leptin at different times of the year. Read More

    Pancreatic α-cell hyperplasia and hyperglucagonemia due to a glucagon receptor splice mutation.
    Endocrinol Diabetes Metab Case Rep 2016 21;2016. Epub 2016 Nov 21.
    Metabolic Disease Research , Novo Nordisk A/S, Måløv , Denmark.
    Glucagon stimulates hepatic glucose production by activating specific glucagon receptors in the liver, which in turn increase hepatic glycogenolysis as well as gluconeogenesis and ureagenesis from amino acids. Conversely, glucagon secretion is regulated by concentrations of glucose and amino acids. Disruption of glucagon signaling in rodents results in grossly elevated circulating glucagon levels but no hypoglycemia. Read More

    Hyperglycemic, high anion-gap metabolic acidosis in patients receiving SGLT-2 inhibitors for diabetes management.
    J Diabetes Complications 2017 Mar 9;31(3):611-614. Epub 2016 Nov 9.
    Department of Medicine, Division of Endocrinology, Diabetes & Metabolism, University of Tennessee Health Science Center, Memphis, TN. Electronic address:
    Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are a class of antidiabetic medications that improve glycemic control via inhibiting the reabsorption of filtered glucose and are approved for use in type 2 diabetes (T2DM). These drugs have recently been associated with euglycemic diabetic ketoacidosis (DKA). An increasing number of cases of SGLT-2i-associated DKA have occurred in patients with T2DM. Read More

    The biology of glucagon and the consequences of hyperglucagonemia.
    Biomark Med 2016 Nov 9;10(11):1141-1151. Epub 2016 Sep 9.
    Department of Biomedical Sciences, Faculty of Health & Medical Sciences, University of Copenhagen, Denmark.
    The proglucagon-derived peptide hormone, glucagon, comprises 29 amino acids. Its secretion from the pancreatic α cells is regulated by several factors. Glucagon increases blood glucose levels through gluconeogenesis and glycogenolysis. Read More

    [Glucagon antagonists open a new way in treatment of type 2 diabetes Mellitus].
    Vnitr Lek Fall 2016;62(7-8):661-6
    Unlabelled: Excessive hepatic glucose production resulting from dysregulated glucagon secretion associated with inappropriate fasting and postprandial hyperglucagonemia is common feature in type 2 diabetes (DM2T). The effects of some currently widely used anti-diabetic agents, especially concerning metformin, GLP1 agonists and inhibitors of DPP4, comprise partial supression of glucagon secretion and/or action. Complete supression of glucagon action is recently widely investigated in experiments, and also results of phase 1 and 2 of the clinical trials are available. Read More

    Seronegative necrolytic acral erythema: A report of two cases and literature review.
    Indian Dermatol Online J 2016 Jul-Aug;7(4):304-7
    Department of Dermatology, Venereology and Leprosy, Shri BM Patil Medical College, Hospital and Research Centre, BLDE University, Bijapur, Karnataka, India.
    Necrolytic acral erythema (NAE) is a newly described entity, seen in patients infected with hepatitis C virus. It is characterized by its distinguishing acral distribution, psoriasiform skin eruption and histological features. Its etiopathogenesis is not fully understood though hypo amino academia, hyperglucagonemia and zinc deficiency are considered as probable causes. Read More

    Postabsorptive hyperglucagonemia in patients with type 2 diabetes mellitus analyzed with a novel enzyme-linked immunosorbent assay.
    J Diabetes Investig 2016 May 24;7(3):324-31. Epub 2015 Aug 24.
    Division of Diabetes, Endocrinology and Metabolism Department of Internal Medicine Hyogo College of Medicine Nishinomiya Hyogo Japan.
    Aims/introduction: The aims of the present study were to investigate the performance of a novel sandwich enzyme-linked immunosorbent assay (ELISA) for measuring glucagon (1-29) with monoclonal antibodies against both the C- and N-terminal regions of glucagon (1-29), and to analyze the differences in plasma levels and responses of glucagon (1-29) to oral glucose loading in normal glucose tolerance (NGT) subjects and patients with type 2 diabetes mellitus.

    Materials And Methods: The cross-reactivity against proglucagon fragments using the ELISA kit and two types of conventional radioimmunoassay (RIA) kits was evaluated. A 75-g oral glucose tolerance test was carried out with NGT subjects and patients with type 2 diabetes mellitus, and the glucagon (1-29) concentration was measured using three types of kit. Read More

    Hyperglucagonemia Mitigates the Effect of Metformin on Glucose Production in Prediabetes.
    Cell Rep 2016 May 5;15(7):1394-400. Epub 2016 May 5.
    Division of Endocrinology, Mayo Clinic, Rochester, MN 55905, USA. Electronic address:
    The therapeutic mechanism of metformin action remains incompletely understood. Whether metformin inhibits glucagon-stimulated endogenous glucose production (EGP), as in preclinical studies, is unclear in humans. To test this hypothesis, we studied nine prediabetic individuals using a randomized, placebo-controlled, double-blinded, crossover study design. Read More

    Hyperglucagonemia in an animal model of insulin- deficient diabetes: what therapy can improve it?
    Clin Diabetes Endocrinol 2016 2;2:11. Epub 2016 May 2.
    Division of Metabolism, Endocrinology & Diabetes, University of Michigan Medical Center, Ann Arbor, MI USA.
    Background: Intra-islet insulin contributes to alpha-cell suppression. Akita mice carry a toxic-gain-of- function Ins2 gene mutation encoding proinsulin-C(A7)Y, similar to that described in human Mutant Ins-gene induced Diabetes of Youth, which decreases intra-islet insulin. Herein, we examined Akita mice for examination of circulating insulin and circulating glucagon levels. Read More

    [Factors modulating food intake and energy expenditure prior to liver transplantation].
    An Sist Sanit Navar 2016 Apr 29;39(1):105-14. Epub 2016 Apr 29.
    Hospital Universitario de Burgos.
    Background: There is a high prevalence of nutritional disorders in patients with liver cirrhosis (LC). This study was designed to assess the relationships between liver function, IFG-I/IGFBP-3, nutritional status, leptin, ghrelin and glucagon in 21 patients waiting for liver transplantation (LT).

    Methods: We studied 21 men aged 56±2. Read More

    Hypothalamic glucagon signaling in fasting hypoglycemia.
    Life Sci 2016 May 12;153:118-23. Epub 2016 Apr 12.
    Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan. Electronic address:
    Aims: Sustained glucagon infusion increases hepatic glucose production, but this effect is transient due to hypothalamic glucagon signaling. In hypoglycemia, glucagon acts as a major defense to sustain the blood glucose level and this raises the question regarding glucagon signaling associated glucose production in prolonged fasting hypoglycemia. In this study, we investigated the proteins associated with hypothalamic glucagon signaling and liver gluconeogenesis during fasting hypoglycemia. Read More

    Activation of the cAMP-PKA pathway Antagonizes Metformin Suppression of Hepatic Glucose Production.
    J Biol Chem 2016 May 21;291(20):10562-70. Epub 2016 Mar 21.
    Departments of Medicine and.
    Metformin is the most commonly prescribed oral anti-diabetic agent worldwide. Surprisingly, about 35% of diabetic patients either lack or have a delayed response to metformin treatment, and many patients become less responsive to metformin over time. It remains unknown how metformin resistance or insensitivity occurs. Read More

    Mechanisms Regulating Insulin Response to Intragastric Glucose in Lean and Non-Diabetic Obese Subjects: A Randomized, Double-Blind, Parallel-Group Trial.
    PLoS One 2016 4;11(3):e0150803. Epub 2016 Mar 4.
    Department of Biomedicine, Division of Gastroenterology, University Hospital Basel, Basel, Switzerland.
    Background/objectives: The changes in blood glucose concentrations that result from an oral glucose challenge are dependent on the rate of gastric emptying, the rate of glucose absorption and the rate of insulin-driven metabolism that include the incretins, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). The rate of insulin-driven metabolism is clearly altered in obese subjects, but it is controversial which of these factors is predominant. We aimed to quantify gastric emptying, plasma insulin, C-peptide, glucagon and glucose responses, as well as incretin hormone secretions in obese subjects and healthy controls during increasing glucose loads. Read More

    Early Alterations in Glycemic Control and Pancreatic Endocrine Function in Nondiabetic Patients With Chronic Pancreatitis.
    Pancreas 2016 Apr;45(4):565-71
    From the Departments *Pediatrics, †Surgery, and ‡Medicine, University of Minnesota, Minneapolis, MN.
    Objectives: Diabetes mellitus is a frequent consequence of chronic pancreatitis (CP). Little is known about pancreatic endocrine function before the development of diabetes mellitus in CP, particularly in females, or those without calcific and/or alcoholic pancreatitis.

    Methods: Twenty-five nondiabetic adult patients with CP (19 female; mean [SE] age, 34. Read More

    GLP-1 Restores Altered Insulin and Glucagon Secretion in Posttransplantation Diabetes.
    Diabetes Care 2016 Apr 23;39(4):617-24. Epub 2016 Feb 23.
    Section of Nephrology, Department of Transplant Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway Metabolic and Renal Research Group, UiT The Arctic University of Norway, Tromsø, Norway.
    Objective: Development of posttransplantation diabetes (PTDM) is characterized by reduced insulin secretion and sensitivity. We aimed to investigate whether hyperglucagonemia could play a role in PTDM and to examine the insulinotropic and glucagonostatic effects of the incretin hormone glucagon-like peptide 1 (GLP-1) during fasting and hyperglycemic conditions, respectively.

    Research Design And Methods: Renal transplant recipients with (n = 12) and without (n = 12) PTDM underwent two separate experimental days with 3-h intravenous infusions of GLP-1 (0. Read More

    MitoNEET-Parkin Effects in Pancreatic α- and β-Cells, Cellular Survival, and Intrainsular Cross Talk.
    Diabetes 2016 Jun 19;65(6):1534-55. Epub 2016 Feb 19.
    Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX Department of Cell Biology, The University of Texas Southwestern Medical Center, Dallas, TX
    Mitochondrial metabolism plays an integral role in glucose-stimulated insulin secretion (GSIS) in β-cells. In addition, the diabetogenic role of glucagon released from α-cells plays a major role in the etiology of both type 1 and type 2 diabetes because unopposed hyperglucagonemia is a pertinent contributor to diabetic hyperglycemia. Titrating expression levels of the mitochondrial protein mitoNEET is a powerful approach to fine-tune mitochondrial capacity of cells. Read More

    Role of growth hormone-releasing hormone in dyslipidemia associated with experimental type 1 diabetes.
    Proc Natl Acad Sci U S A 2016 Feb 1;113(7):1895-900. Epub 2016 Feb 1.
    Endocrine, Polypeptide, and Cancer Institute, Veterans Affairs Medical Center, Miami, FL 33125; Department of Pathology, Miller School of Medicine, University of Miami, Miami, FL 33136; Division of Hematology and Oncology, Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL 33136; Division of Endocrinology, Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL 33136
    Dyslipidemia associated with triglyceride-rich lipoproteins (TRLs) represents an important residual risk factor for cardiovascular and chronic kidney disease in patients with type 1 diabetes (T1D). Levels of growth hormone (GH) are elevated in T1D, which aggravates both hyperglycemia and dyslipidemia. The hypothalamic growth hormone-releasing hormone (GHRH) regulates the release of GH by the pituitary but also exerts separate actions on peripheral GHRH receptors, the functional role of which remains elusive in T1D. Read More

    Euglycemia Restoration by Central Leptin in Type 1 Diabetes Requires STAT3 Signaling but Not Fast-Acting Neurotransmitter Release.
    Diabetes 2016 Apr 28;65(4):1040-9. Epub 2016 Jan 28.
    Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases of McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX
    Central leptin action is sufficient to restore euglycemia in insulinopenic type 1 diabetes (T1D); however, the underlying mechanism remains poorly understood. To examine the role of intracellular signal transducer and activator of transcription 3 (STAT3) pathways, we used LepRs/s mice with disrupted leptin-phosphorylated STAT3 signaling to test the effect of central leptin on euglycemia restoration. These mice developed streptozocin-induced T1D, which was surprisingly not associated with hyperglucagonemia, a typical manifestation in T1D. Read More

    Effects of endogenous GLP-1 and GIP on glucose tolerance after Roux-en-Y gastric bypass surgery.
    Am J Physiol Endocrinol Metab 2016 Apr 19;310(7):E505-14. Epub 2016 Jan 19.
    Department of Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark; NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;
    Exaggerated secretion of glucagon-like peptide 1 (GLP-1) is important for postprandial glucose tolerance after Roux-en-Y gastric bypass (RYGB), whereas the role of glucose-dependent insulinotropic polypeptide (GIP) remains to be resolved. We aimed to explore the relative importance of endogenously secreted GLP-1 and GIP on glucose tolerance and β-cell function after RYGB. We used DPP-4 inhibition to enhance concentrations of intact GIP and GLP-1 and the GLP-1 receptor antagonist exendin-(9-39) (Ex-9) for specific blockage of GLP-1 actions. Read More

    Defective insulin secretion by chronic glucagon receptor activation in glucose intolerant mice.
    J Endocrinol 2016 Mar 23;228(3):171-8. Epub 2015 Dec 23.
    Department of Clinical SciencesBiomedical Center, Lund University, SE 22184 Lund, SwedenZealand Pharma A/SResearch and Development, DK-2600 Glostrup, Denmark.
    Stimulation of insulin secretion by short-term glucagon receptor (GCGR) activation is well characterized; however, the effect of long-term GCGR activation on β-cell function is not known, but of interest, since hyperglucagonemia occurs early during development of type 2 diabetes. Therefore, we examined whether chronic GCGR activation affects insulin secretion in glucose intolerant mice. To induce chronic GCGR activation, high-fat diet fed mice were continuously (2 weeks) infused with the stable glucagon analog ZP-GA-1 and challenged with oral glucose and intravenous glucose±glucagon-like peptide 1 (GLP1). Read More

    Evidence of Extrapancreatic Glucagon Secretion in Man.
    Diabetes 2016 Mar 15;65(3):585-97. Epub 2015 Dec 15.
    Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark The Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
    Glucagon is believed to be a pancreas-specific hormone, and hyperglucagonemia has been shown to contribute significantly to the hyperglycemic state of patients with diabetes. This hyperglucagonemia has been thought to arise from α-cell insensitivity to suppressive effects of glucose and insulin combined with reduced insulin secretion. We hypothesized that postabsorptive hyperglucagonemia represents a gut-dependent phenomenon and subjected 10 totally pancreatectomized patients and 10 healthy control subjects to a 75-g oral glucose tolerance test and a corresponding isoglycemic intravenous glucose infusion. Read More

    [Significance of the regulation of hyperglucagonemia in type 2 diabetes mellitus].
    Nihon Rinsho 2015 Dec;73(12):1988-94
    Abstract Generally, pancreatic β-cell dysfunction and hypoinsulinemia have been known as the cause of development of hyperglycemia in diabetes mellitus. Pancreatic α-cell dysfunction, particularly hyperglucagonemia is also serious problem to increase hepatic glucose production in type 2 diabetes mellitus (T2DM). β-cell mass decrement and α-cell mass increment in T2DM have been reported in many reports inclusive of our study. Read More

    Prediabetes linked to excess glucagon in transgenic mice with pancreatic active AKT1.
    J Endocrinol 2016 Jan 20;228(1):49-59. Epub 2015 Oct 20.
    Burnett School of Biomedical SciencesCollege of Medicine, University of Central Florida, 6900 Lake Nona Boulevard, Orlando, Florida 32827, USADepartment of Head and Neck SurgeryThe Greater Poland Cancer Centre, 61-866 Poznan, Poland
    Protein kinase B/AKT has three isoforms (AKT1-3) and is renowned for its central role in the regulation of cell growth and proliferation, due to its constitutive activation in various cancers. AKT2, which is highly expressed in insulin-responsive tissues, has been identified as a primary regulator of glucose metabolism as Akt2 knockout mice (Akt2(-/-)) are glucose-intolerant and insulin-resistant. However, the role of AKT1 in glucose metabolism is not as clearly defined. Read More

    The Impact of Chronic Liraglutide Therapy on Glucagon Secretion in Type 2 Diabetes: Insight From the LIBRA Trial.
    J Clin Endocrinol Metab 2015 Oct 31;100(10):3702-9. Epub 2015 Jul 31.
    Leadership Sinai Centre for Diabetes (C.K.K., B.Z., H.C., R.R.) and Lunenfeld-Tanenbaum Research Institute (B.Z., R.R.), Mount Sinai Hospital, Toronto, Ontario M5T 3L9, Canada; Division of Endocrinology (C.K.K., B.Z., P.W.C., R.R.), University of Toronto, Toronto, Ontario M5S 2J7, Canada; and Keenan Research Centre for Biomedical Science of St Michael's Hospital (P.W.C.), Toronto, Ontario M5B 1W8, Canada.
    Context: In patients with type 2 diabetes (T2DM), impaired suppression of postprandial glucagonemia is a metabolic defect that contributes to hyperglycemia. Treatment with a glucagon-like peptide-1 agonist can reduce hyperglucagonemia in the acute setting, but little is known about the durability of this effect with long-term treatment.

    Objective: The purpose of this study was to evaluate the impact of chronic liraglutide therapy on glucagon regulation in early T2DM. Read More

    Successful pharmaceutical-grade streptozotocin (STZ)-induced hyperglycemia in a conscious tethered baboon (Papio hamadryas) model.
    J Med Primatol 2015 Aug 30;44(4):202-17. Epub 2015 Jun 30.
    Southwest National Primate Research Center, San Antonio, TX, USA.
    Background: Non-human primate (NHP) diabetic models using chemical ablation of β-cells with STZ have been achieved by several research groups. Chemotherapeutic STZ could lead to serious adverse events including nephrotoxicity, hepatotoxicity, and mortality.

    Methods: We implemented a comprehensive therapeutic strategy that included the tether system, permanent indwelling catheter implants, an aggressive hydration protocol, management for pain with IV nubain and anxiety with IV midazolam, moment-by-moment monitoring of glucose levels post-STZ administration, and continuous intravenous insulin therapy. Read More

    Effect of Short-term Intensive Insulin Therapy on Post-challenge Hyperglucagonemia in Early Type 2 Diabetes.
    J Clin Endocrinol Metab 2015 Aug 16;100(8):2987-95. Epub 2015 Jun 16.
    Leadership Sinai Centre for Diabetes (C.K.K., B.Z., H.C., R.R.), Mt Sinai Hospital, Toronto, ON M5T 3L9, Canada; Division of Endocrinology (C.K.K., B.Z., R.R.), University of Toronto, Toronto, ON M5G 2C4, Canada; and Lunenfeld-Tanenbaum Research Institute (B.Z., R.R.), Mt Sinai Hospital, Toronto, ON M5G 1X5, Canada.
    Context: Hyperglucagonemia is a characteristic feature of type 2 diabetes (T2DM) that has been postulated to be due to β-cell dysfunction and the resultant loss of insulin-mediated α-cell suppression. When administered in early T2DM, short-term intensive insulin therapy (IIT) can improve β-cell function, resulting in reduced glycemic variability.

    Objective: To evaluate the impact of IIT on hyperglucagonemia and its associations with β-cell function and glycemic variability. Read More

    Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment With Sodium-Glucose Cotransporter 2 Inhibition.
    Diabetes Care 2015 Sep 15;38(9):1687-93. Epub 2015 Jun 15.
    University of Washington School of Medicine, Seattle, WA.
    Objective: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are the most recently approved antihyperglycemic medications. We sought to describe their association with euglycemic diabetic ketoacidosis (euDKA) in hopes that it will enhance recognition of this potentially life-threatening complication.

    Research Design And Methods: Cases identified incidentally are described. Read More

    Glucagon Receptor Blockade With a Human Antibody Normalizes Blood Glucose in Diabetic Mice and Monkeys.
    Endocrinology 2015 Aug 28;156(8):2781-94. Epub 2015 May 28.
    Regeneron Pharmaceuticals, Inc, Tarrytown, New York 10591.
    Antagonizing glucagon action represents an attractive therapeutic option for reducing hepatic glucose production in settings of hyperglycemia where glucagon excess plays a key pathophysiological role. We therefore generated REGN1193, a fully human monoclonal antibody that binds and inhibits glucagon receptor (GCGR) signaling in vitro. REGN1193 administration to diabetic ob/ob and diet-induced obese mice lowered blood glucose to levels observed in GCGR-deficient mice. Read More

    Glucagon receptor gene mutations with hyperglucagonemia but without the glucagonoma syndrome.
    World J Gastrointest Surg 2015 Apr;7(4):60-6
    Helen C Miller, Panagiotis Drymousis, Andrea Frilling, Department of Surgery and Cancer, Imperial College London, London W12 0HS, United Kingdom.
    Pancreatic neoplasms producing exclusively glucagon associated with glucagon cell hyperplasia of the islets and not related to hereditary endocrine syndromes have been recently described. They represent a novel entity within the panel of non-syndromic disorders associated with hyperglucagonemia. This case report describes a 36-year-old female with a 10 years history of non-specific abdominal pain. Read More

    Inhibition of the glucose transporter SGLT2 with dapagliflozin in pancreatic alpha cells triggers glucagon secretion.
    Nat Med 2015 May 20;21(5):512-7. Epub 2015 Apr 20.
    1] European Genomic Institute for Diabetes, Lille, France. [2] INSERM UMR 1190, Lille, France. [3] Centre Hospitalier Régional Universitaire, Lille, France. [4] Université de Lille, Lille, France.
    Type 2 diabetes (T2D) is characterized by chronic hyperglycemia resulting from a deficiency in insulin signaling, because of insulin resistance and/or defects in insulin secretion; it is also associated with increases in glucagon and endogenous glucose production (EGP). Gliflozins, including dapagliflozin, are a new class of approved oral antidiabetic agents that specifically inhibit sodium-glucose co-transporter 2 (SGLT2) function in the kidney, thus preventing renal glucose reabsorption and increasing glycosuria in diabetic individuals while reducing hyperglycemia. However, gliflozin treatment in subjects with T2D increases both plasma glucagon and EGP by unknown mechanisms. Read More

    Influence of gastrointestinal factors on glucose metabolism in patients with cirrhosis.
    J Gastroenterol Hepatol 2015 Oct;30(10):1522-8
    Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
    Background And Aim: The impaired glucose tolerance in cirrhosis is poorly understood. We evaluated the influence of gastrointestinal-mediated glucose disposal and incretin effect in patients with cirrhosis.

    Methods: Non-diabetic patients with Child-Pugh A or B cirrhosis (n = 10) and matched healthy controls (n = 10) underwent a 50-g oral glucose tolerance test (OGTT) and an isoglycemic intravenous glucose infusion. Read More

    Glucagon--Early breakthroughs and recent discoveries.
    Peptides 2015 May 23;67:74-81. Epub 2015 Mar 23.
    Department of Clinical Sciences Lund, Lund University, Lund, Sweden. Electronic address:
    Glucagon was discovered in 1922 as a hyperglycemic factor in the pancreas. During its early history up to 1970, glucagon was shown to increase circulating glucose through stimulating glycogenolysis in the liver. It was also shown to be a constituent of islet non-β cells and to signal through G protein coupled receptors and cyclic AMP. Read More

    [Significance of glucagon control in the diabetes treatment].
    Nihon Rinsho 2015 Mar;73(3):509-16
    Among islet cell types, much less attention has been paid to α cells than to β cells, but glucagon, the product of α cells, has been shown to play a major role in the development of hyperglycemia in T2DM. Recent clinical application of DPP4 inhibitor and GLP-1 receptor agonist gave attention to glucagon again. Furthermore, recently metformin has been also reported to suppress glucagon's function on hepatic glucose production. Read More

    Incretin and glucagon levels in adult offspring exposed to maternal diabetes in pregnancy.
    J Clin Endocrinol Metab 2015 May 17;100(5):1967-75. Epub 2015 Mar 17.
    Center for Pregnant Women with Diabetes (L.K., T.D.C., E.R.M., P.D.) and Departments of Obstetrics (L.K., P.D.) and Endocrinology (E.R.M.), Rigshospitalet, DK-2100 Copenhagen, Denmark; Department of Gynaecology and Obstetrics (T.D.C.), Nordsjaellands Hospital, 3400 Hillerød, Denmark; Institute of Clinical Medicine (E.R.M., P.D.), Faculty of Health Science, University of Copenhagen, 2200 Copenhagen, Denmark; Novo Nordisk Foundation (NNF) Center for Basic Metabolic Research (T.H.), Section of Metabolic Genetics, University of Copenhagen, 2200 Copenhagen, Denmark; Faculty of Health Sciences (T.H.), University of Southern Denmark, 5230 Odense M, Denmark; and NNF Center for Basic Metabolic Research and Department of Biomedical Sciences (J.J.H.), University of Copenhagen, 2200 Copenhagen, Denmark.
    Context: Fetal exposure to maternal diabetes is associated with increased risk of type 2 diabetes mellitus (T2DM) later in life. The pathogenesis of T2DM involves dysfunction of the incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), as well as hyperglucagonemia.

    Objective: Our aim was to investigate circulating plasma levels of GLP-1, GIP, and glucagon during the oral glucose tolerance test (OGTT) in adult offspring of women with diabetes in pregnancy. Read More

    Pancreatic α-Cell Dysfunction in Type 2 Diabetes: Old Kids on the Block.
    Diabetes Metab J 2015 Feb;39(1):1-9
    Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea.
    Type 2 diabetes (T2D) has been known as 'bi-hormonal disorder' since decades ago, the role of glucagon from α-cell has languished whereas β-cell taking center stage. Recently, numerous findings indicate that the defects of glucagon secretion get involve with development and exacerbation of hyperglycemia in T2D. Aberrant α-cell responses exhibit both fasting and postprandial states: hyperglucagonemia contributes to fasting hyperglycemia caused by inappropriate hepatic glucose production, and to postprandial hyperglycemia owing to blunted α-cell suppression. Read More

    Advances in pathology of diabetes from pancreatic islets to neuropathy--a tribute to Paul Langerhans.
    Pathol Int 2015 Apr 23;65(4):157-69. Epub 2015 Feb 23.
    Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
    There emerges a world epidemic of diabetes, afflicting over 3.8 billion people globally. The socio-economic burden of this disorder is tremendous and there is an urgent need to solve the problems incurred from this disorder and to establish an efficient way of prevention and treatment. Read More

    Glucagon receptor antibody completely suppresses type 1 diabetes phenotype without insulin by disrupting a novel diabetogenic pathway.
    Proc Natl Acad Sci U S A 2015 Feb 9;112(8):2503-8. Epub 2015 Feb 9.
    Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390; Department of Medical Service, Veteran's Administration North Texas Health Care System, Dallas, TX 75216
    Insulin monotherapy can neither maintain normoglycemia in type 1 diabetes (T1D) nor prevent the long-term damage indicated by elevated glycation products in blood, such as glycated hemoglobin (HbA1c). Here we find that hyperglycemia, when unaccompanied by an acute increase in insulin, enhances itself by paradoxically stimulating hyperglucagonemia. Raising glucose from 5 to 25 mM without insulin enhanced glucagon secretion ∼two- to fivefold in InR1-G9 α cells and ∼18-fold in perfused pancreata from insulin-deficient rats with T1D. Read More

    Recent Progress in the Use of Glucagon and Glucagon Receptor Antago-nists in the Treatment of Diabetes Mellitus.
    Open Med Chem J 2014 31;8:28-35. Epub 2014 Dec 31.
    Department of Anatomy, College of Medicine & Health Sciences, United Arab Emirates University, Al Ain, United Ar-ab Emirates.
    Glucagon is an important pancreatic hormone, released into blood circulation by alpha cells of the islet of Langerhans. Glucagon induces gluconeogenesis and glycogenolysis in hepatocytes, leading to an increase in hepatic glucose production and subsequently hyperglycemia in susceptible individuals. Hyperglucagonemia is a constant feature in patients with T2DM. Read More

    Evidence That in Uncontrolled Diabetes, Hyperglucagonemia Is Required for Ketosis but Not for Increased Hepatic Glucose Production or Hyperglycemia.
    Diabetes 2015 Jul 29;64(7):2376-87. Epub 2015 Jan 29.
    Diabetes and Obesity Center of Excellence, Department of Medicine, University of Washington, Seattle, WA
    Several lines of evidence implicate excess glucagon secretion in the elevated rates of hepatic glucose production (HGP), hyperglycemia, and ketosis characteristic of uncontrolled insulin-deficient diabetes (uDM), but whether hyperglucagonemia is required for hyperglycemia in this setting is unknown. To address this question, adult male Wistar rats received either streptozotocin (STZ) to induce uDM (STZ-DM) or vehicle and remained nondiabetic. Four days later, animals received daily subcutaneous injections of either the synthetic GLP-1 receptor agonist liraglutide in a dose-escalating regimen to reverse hyperglucagonemia or its vehicle for 10 days. Read More

    Liraglutide reduces the body weight and waist circumference in Chinese overweight and obese type 2 diabetic patients.
    Acta Pharmacol Sin 2015 Feb 26;36(2):200-8. Epub 2015 Jan 26.
    2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Key Laboratory of Hormone and Development (Ministry of Health), Metabolic Disease Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
    Aim: To investigate the effects of liraglutide, a glucagon-like peptide-1 (GLP-1) receptor activator, on body weight and waist circumference in Chinese overweight and obese type 2 diabetic patients.

    Methods: A total of 328 Chinese overweight and obese type 2 diabetic patients were included in this multi-center, open-labeled and self-controlled clinical study. The patients were subcutaneously injected with liraglutide once daily for 24 weeks as add-on therapy to their previous hypoglycemic treatments. Read More

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