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    659 results match your criteria Hyperglucagonemia

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    Glucagon promotes colon cancer cell growth via regulating AMPK and MAPK pathways.
    Oncotarget 2018 Feb 31;9(12):10650-10664. Epub 2018 Jan 31.
    Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan.
    Cancer is one of the major causes of death in diabetic patients, and an association between antidiabetic drugs and cancer risk has been reported. Such evidence implies a strong connection between diabetes and cancer. Recently, glucagon has been recognized as a pivotal factor implicated in the pathophysiology of diabetes. Read More

    Glucagon Receptor Antagonism Improves Glucose Metabolism and Cardiac Function by Promoting AMP-Mediated Protein Kinase in Diabetic Mice.
    Cell Rep 2018 Feb;22(7):1760-1773
    Touchstone Diabetes Center, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8549, USA. Electronic address:
    The antidiabetic potential of glucagon receptor antagonism presents an opportunity for use in an insulin-centric clinical environment. To investigate the metabolic effects of glucagon receptor antagonism in type 2 diabetes, we treated Lepr and Lep mice with REMD 2.59, a human monoclonal antibody and competitive antagonist of the glucagon receptor. Read More

    In Uncontrolled Diabetes, Hyperglucagonemia and Ketosis Result From Deficient Leptin Action in the Parabrachial Nucleus.
    Endocrinology 2018 Apr;159(4):1585-1594
    University of Washington Medicine Diabetes Institute, Department of Medicine, University of Washington, Seattle, Washington.
    Growing evidence implicates neurons that project from the lateral parabrachial nucleus (LPBN) to the hypothalamic ventromedial nucleus (VMN) in a neurocircuit that drives counterregulatory responses to hypoglycemia, including increased glucagon secretion. Among LPBN neurons in this circuit is a subset that expresses cholecystokinin (LPBNCCK neurons) and is tonically inhibited by leptin. Because uncontrolled diabetes is associated with both leptin deficiency and hyperglucagonemia, and because intracerebroventricular (ICV) leptin administration reverses both hyperglycemia and hyperglucagonemia in this setting, we hypothesized that deficient leptin inhibition of LPBNCCK neurons drives activation of this LPBN→VMN circuit and thereby results in hyperglucagonemia. Read More

    α-cell glucokinase suppresses glucose-regulated glucagon secretion.
    Nat Commun 2018 02 7;9(1):546. Epub 2018 Feb 7.
    Center for Integrative Genomics, University of Lausanne, 1015, Lausanne, Switzerland.
    Glucagon secretion by pancreatic α-cells is triggered by hypoglycemia and suppressed by high glucose levels; impaired suppression of glucagon secretion is a hallmark of both type 1 and type 2 diabetes. Here, we show that α-cell glucokinase (Gck) plays a role in the control of glucagon secretion. Using mice with α-cell-specific inactivation of Gck (αGckKO mice), we find that glucokinase is required for the glucose-dependent increase in intracellular ATP/ADP ratio and the closure of K channels in α-cells and the suppression of glucagon secretion at euglycemic and hyperglycemic levels. Read More

    Alpha cell dysfunction in type 1 diabetes.
    Peptides 2018 Feb;100:54-60
    Department of Pharmacology and Physiology, Saint Louis University School of Medicine, 1402 S. Grand Blvd, Saint Louis, MO 63104, United States. Electronic address:
    Type 1 diabetes is characterized by selective loss of beta cells and insulin secretion, which significantly impact glucose homeostasis. However, this progressive disease is also associated with dysfunction of the alpha cell component of the islet, which can exacerbate hyperglycemia due to paradoxical hyperglucagonemia or lead to severe hypoglycemia as a result of failed counterregulation. In this review, the physiology of alpha cell secretion and the potential mechanisms underlying alpha cell dysfunction in type 1 diabetes will be explored. Read More

    Glucagon receptor signaling in metabolic diseases.
    Peptides 2018 Feb;100:42-47
    Department of Biomedical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, and the Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark. Electronic address:
    Glucagon is a peptide hormone secreted from the pancreatic alpha cells in response to hypoglycemia but in some patients with type 2 diabetes a paradoxical hypersecretion results from the intake of glucose. In rodent, antagonizing the actions of glucagon have been shown to be effective for lowering blood glucose levels and this has recently have been solidified in patients with type 2 diabetes. Although the reported increases of liver enzymes, hyperglucagonemia, and alpha cell hyperplasia resulting from glucagon receptor antagonism may potentially limit the clinical applicability of glucagon receptor antagonists, they may serve as an instrumental toolbox for delineating the physiology of glucagon. Read More

    IAPP and type 1 diabetes: implications for immunity, metabolism and islet transplants.
    J Mol Endocrinol 2018 Feb;60(2):R57-R75
    Department of SurgeryBC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
    Islet amyloid polypeptide (IAPP), the main component of islet amyloid in type 2 diabetes and islet transplants, is now recognized as a contributor to beta cell dysfunction. Increasingly, evidence warrants its investigation in type 1 diabetes owing to both its immunomodulatory and metabolic actions. Autoreactive T cells to IAPP-derived epitopes have been described in humans, suggesting that IAPP is an islet autoantigen in type 1 diabetes. Read More

    Patterns of Plasma Glucagon Dynamics Do Not Match Metabolic Phenotypes in Young Women.
    J Clin Endocrinol Metab 2018 Mar;103(3):972-982
    Diabetes Research Group, Medizinische Klinik IV, Medical Center of the University of Munich (Klinikum der Universitaet Muenchen), Munich, Germany.
    Context: The role of hyperglucagonemia in type 2 diabetes is still debated.

    Objective: We analyzed glucagon dynamics during oral glucose tolerance tests (oGTTs) in young women with one out of three metabolic phenotypes: healthy control (normoglycemic after a normoglycemic pregnancy), normoglycemic high-risk (normoglycemic after a pregnancy complicated by gestational diabetes), and prediabetes/screening-diagnosed type 2 diabetes. We asked if glucagon patterns were homogeneous within the metabolic phenotypes. Read More

    Metabolic regulation of GLP-1 and PC1/3 in pancreatic α-cell line.
    PLoS One 2017 9;12(11):e0187836. Epub 2017 Nov 9.
    Department of Clinical and Experimental Medicine, Section of Diabetes and Metabolic Diseases, University of Pisa - Cisanello Hospital, Pisa, Italy.
    Background And Aims: An intra-islet incretin system has been recently suggested to operate through modulation of the expression and activity of proconvertase 1/3 and 2 (PC1/3, PC2) in pancreatic alpha-cell accounting for local release of GLP-1. Little is known, whether this alpha-cell activity can be affected by the metabolic alterations occurring in type 2 diabetes, such as hyperglycemia, hyperlipidemia or hyperglucagonemia.

    Materials And Methods: AlphaTC1/6 cells from a mice pancreatic cell line were incubated in the presence of two glucose (G) concentration (5. Read More

    Circulating Glucagon 1-61 Regulates Blood Glucose by Increasing Insulin Secretion and Hepatic Glucose Production.
    Cell Rep 2017 Nov;21(6):1452-1460
    Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark. Electronic address:
    Glucagon is secreted from pancreatic α cells, and hypersecretion (hyperglucagonemia) contributes to diabetic hyperglycemia. Molecular heterogeneity in hyperglucagonemia is poorly investigated. By screening human plasma using high-resolution-proteomics, we identified several glucagon variants, among which proglucagon 1-61 (PG 1-61) appears to be the most abundant form. Read More

    Measurement of Gastrointestinal Hormones.
    Dan Med J 2017 Nov;64(11)
    Towards the end of the 20th century, the number of subjects with diabetes and obesity rose exponentially. The discoveries of insulin- and appetite-modulating chemical signals, including glucagon-like peptide-1 (GLP-1), secreted from the gastrointestinal system, led to development of a new group of drugs which now are being used for glucose-lowering therapy and weight loss. Understanding of the physiology of gut derived signals and their pathophysiologi-cal importance requires accurate measurements of their circulat-ing levels. Read More

    Current Therapies That Modify Glucagon Secretion: What Is the Therapeutic Effect of Such Modifications?
    Curr Diab Rep 2017 Oct 28;17(12):128. Epub 2017 Oct 28.
    Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
    Purpose Of Review: Hyperglucagonemia contributes significantly to hyperglycemia in type 2 diabetes and suppressed glucagon levels may increase the risk of hypoglycemia. Here, we give a brief overview of glucagon physiology and the role of glucagon in the pathophysiology of type 2 diabetes and provide insights into how antidiabetic drugs influence glucagon secretion as well as a perspective on the future of glucagon-targeting drugs.

    Recent Findings: Several older as well as recent investigations have evaluated the effect of antidiabetic agents on glucagon secretion to understand how glucagon may be involved in the drugs' efficacy and safety profiles. Read More

    Lipid nanoparticle delivery of glucagon receptor siRNA improves glucose homeostasis in mouse models of diabetes.
    Mol Metab 2017 Oct 22;6(10):1161-1172. Epub 2017 Jun 22.
    Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada; Department of Surgery, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada. Electronic address:
    Objective: Hyperglucagonemia is present in many forms of diabetes and contributes to hyperglycemia, and glucagon suppression can ameliorate diabetes in mice. Leptin, a glucagon suppressor, can also reverse diabetes in rodents. Lipid nanoparticle (LNP) delivery of small interfering RNA (siRNA) effectively targets the liver and is in clinical trials for the treatment of various diseases. Read More

    Glucagon, a key factor in the pathophysiology of type 2 diabetes.
    Biochimie 2017 Dec 9;143:33-36. Epub 2017 Oct 9.
    Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Inserm U567, Département Endocrinologie, Métabolisme et Diabète, 24 rue du Faubourg Saint-Jacques, 75014 Paris, France. Electronic address:
    Excessive circulating glucagon levels have been reported in all forms of diabetes, clinical or experimental. The hyperglucagonemia of diabetes results from an excessive secretion of the hormone secondary from a deficit in insulin secretion and/or a dysfunction of various cells within the islets of Langerhans (somatostatin) leading to the notion of "paracrinopathy". Hyperglucagonemia contributes to the fasting and postprandial hyperglycemia in diabetic patients through an increased hepatic glucose production (mainly gluconeogenesis). Read More

    Disruption of glucagon receptor signaling causes hyperaminoacidemia exposing a possible liver-alpha-cell axis.
    Am J Physiol Endocrinol Metab 2018 01 3;314(1):E93-E103. Epub 2017 Oct 3.
    Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen , Denmark.
    Glucagon secreted from the pancreatic alpha-cells is essential for regulation of blood glucose levels. However, glucagon may play an equally important role in the regulation of amino acid metabolism by promoting ureagenesis. We hypothesized that disruption of glucagon receptor signaling would lead to an increased plasma concentration of amino acids, which in a feedback manner stimulates the secretion of glucagon, eventually associated with compensatory proliferation of the pancreatic alpha-cells. Read More

    Hyperglucagonemia correlates with plasma levels of non-branched-chain amino acids in patients with liver disease independent of type 2 diabetes.
    Am J Physiol Gastrointest Liver Physiol 2018 01 28;314(1):G91-G96. Epub 2017 Sep 28.
    Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
    Patients with type 2 diabetes (T2D) and patients with nonalcoholic fatty liver disease (NAFLD) frequently exhibit elevated plasma concentrations of glucagon (hyperglucagonemia). Hyperglucagonemia and α-cell hyperplasia may result from elevated levels of plasma amino acids when glucagon's action on hepatic amino acid metabolism is disrupted. We therefore measured plasma levels of glucagon and individual amino acids in patients with and without biopsy-verified NAFLD and with and without type T2D. Read More

    Higher glucagon-to-insulin ratio is associated with elevated glycated hemoglobin levels in type 2 diabetes patients.
    Korean J Intern Med 2017 Sep 8. Epub 2017 Sep 8.
    Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
    Background/aims: The importance of α-cell dysfunction in the pathogenesis of type 2 diabetes has re-emerged recently. However, data on whether relative glucagon excess is present in clinical settings are scarce. We aimed to investigate associations between glucagon-to-insulin ratio and various metabolic parameters. Read More

    3-Iodothyronamine reduces insulin secretion in vitro via a mitochondrial mechanism.
    Mol Cell Endocrinol 2018 Jan 25;460:219-228. Epub 2017 Jul 25.
    Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Institut für Experimentelle Endokrinologie, 13353 Berlin, Germany. Electronic address:
    Purpose: 3-iodothyronamine (3-TAM), a decarboxylated and deiodinated thyroid hormone metabolite, leads at pharmacological doses to hypoinsulinemia, hyperglucagonemia and hyperglycemia in vivo. As the pancreatic Langerhans islets express thyroid hormone transmembrane transporters (THTT), we tested the hypothesis that not only plasma membrane-mediated 3-TAM binding to and activation of G-protein coupled receptors, but also 3-TAM metabolite(s) generated by 3-TAM uptake and metabolism might decrease glucose-stimulated insulin secretion (GSIS).

    Methods: Murine pancreatic β-cells MIN6 were characterized for gene expression of THTT, deiodinases and monoamine oxidases. Read More

    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 Oct 31;61(10). Epub 2017 Jul 31.
    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 Erythematosus Patients Despite Normal Glucose Tolerance.
    Arthritis Care Res (Hoboken) 2018 Jan 6;70(1):114-124. Epub 2017 Dec 6.
    Universidade de Sao Paulo, 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 with mild/inactive SLE (SLE group) and 16 age- and body mass index-matched female healthy controls (CTRL group) underwent an MTT and were assessed for insulin sensitivity and beta cell function. Skeletal muscle protein expressions of total and membrane insulin-dependent glucose transporter 4 (GLUT-4) were also evaluated (SLE group: n = 10, CTRL group: 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 03 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 05 5;15(7):1394-1400. 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. mice carry a toxic-gain-of- function gene mutation encoding proinsulin-C(A7)Y, similar to that described in human Mutant -gene induced Diabetes of Youth, which decreases intra-islet insulin. Herein, we examined 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 04 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 06 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 04 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

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