Search Our Scientific Publications & Authors

Sci Rep 2019 Apr 4;9(1):5646. Epub 2019 Apr 4.

Department of Endocrinology, PGIMER Chandigarh, Sector 12, Chandigarh, 160012, India.

Impaired insulin sensitivity (IS) and β-cell dysfunction result in hyperglycaemia in patients of acromegaly. However, alterations in incretins and their impact on glucose-insulin homeostasis in these patients still remain elusive. Twenty patients of active acromegaly (10 each, with and without diabetes) underwent hyperinsulinemic euglycaemic clamp and mixed meal test, before and after surgery, to measure indices of IS, β-cell function, GIP, GLP-1 and glucagon response. Read More

Endocr Rev 2019 Mar 28. Epub 2019 Mar 28.

Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Both type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) strongly associate with increasing body mass index (BMI) and together these metabolic diseases affect millions of individuals. In patients with T2D, increased secretion of glucagon (hyperglucagonemia) contributes to the diabetic hyperglycemia as proven by the significant lowering of fasting plasma glucose levels following glucagon receptor antagonist (GRA) administration. Emerging data now indicate that the elevated plasma concentrations of glucagon may also be associated with hepatic steatosis and not necessarily with the presence or absence of T2D. Read More

Diabetes 2019 May 4;68(5):939-946. Epub 2019 Mar 4.

Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia

Insulin and glucagon exert opposing actions on glucose metabolism, and their secretion is classically viewed as being inversely regulated. This is, however, context specific as protein ingestion concomitantly stimulates euglycemic insulin and glucagon secretion. It remains enigmatic how euglycemia is preserved under these conditions. Read More

Am J Physiol Endocrinol Metab 2019 Apr 26;316(4):E660-E673. Epub 2019 Feb 26.

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen , Denmark.

Glucagon and insulin are important regulators of blood glucose. The importance of insulin receptor signaling for alpha-cell secretion and of glucagon receptor signaling for beta-cell secretion is widely discussed and of clinical interest. Amino acids are powerful secretagogues for both hormones, and glucagon controls amino acid metabolism through ureagenesis. Read More

J Endocrinol 2019 Feb 1. Epub 2019 Feb 1.

L Eliasson, Dept Clinical Sciences in Malmö, Lunds Universitet, Malmö, 214 28, Sweden.

Cystic fibrosis-related diabetes (CFRD) is a common complication for patients with cystic fibrosis (CF), a disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). The cause of CFRD is unclear, but a commonly observed reduction in first-phase insulin secretion suggests defects at the beta cell level. Here we aimed to examine beta- and alpha-cell function in the Cftrtm1EUR/F508del mouse model (C57BL/6J), which carries the most common human mutation in CFTR, the F508del mutation. Read More

Nat Commun 2019 02 1;10(1):548. Epub 2019 Feb 1.

Departments of Internal Medicine, Yale University School of Medicine, P.O. Box 208020, TAC S269, New Haven, CT, 06519, USA.

Sodium-glucose transport protein 2 (SGLT2) inhibitors are a class of anti-diabetic agents; however, concerns have been raised about their potential to induce euglycemic ketoacidosis and to increase both glucose production and glucagon secretion. The mechanisms behind these alterations are unknown. Here we show that the SGLT2 inhibitor (SGLT2i) dapagliflozin promotes ketoacidosis in both healthy and type 2 diabetic rats in the setting of insulinopenia through increased plasma catecholamine and corticosterone concentrations secondary to volume depletion. Read More

J Endocr Soc 2019 Jan 3;3(1):273-283. Epub 2018 Dec 3.

Diabetes Centre, Khoo Teck Puat Hospital, Republic of Singapore.

Background And Aim: The kidney is the main site for glucagon clearance. However, a recent study showed that hyperglucagonemia in patients with end-stage renal disease might not be caused by full-length intact glucagon. Additionally, the relationship between glucagon and renal function in early-stage chronic kidney disease (CKD) has not yet been characterized. Read More

Int J Obes (Lond) 2018 Nov 19. Epub 2018 Nov 19.

Department of Surgical, Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy.

Objective: To evaluate the effect of periodontitis (PD) on glucoregulatory hormones in obesity, never explored so far, a cross-sectional study was conducted in 110 severely obese, non-diabetic individuals.

Methods: We collected clinical periodontal parameters, including probing pocket depth (PPD), bleeding on probing (BOP), clinical attachment level (CAL). Insulin, glucagon, GLP-1 and GIP were measured after 3 days of standardized diet. Read More

Metab Syndr Relat Disord 2018 12 16;16(10):530-536. Epub 2018 Oct 16.

1 Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, Gentofte Hospital, Hellerup, Denmark .

Background: Fasting hyperglucagonemia can be detrimental to glucose metabolism in patients with type 2 diabetes (T2D) and may contribute to metabolic disturbances in obese and/or prediabetic subjects. However, the mechanisms underlying fasting hyperglucagonemia remain elusive.

Methods: We evaluated the interrelationship between fasting hyperglucagonemia and demographic and biochemical parameters in 106 patients with T2D (31% female, age: 57 ± 9 years [mean ± standard deviation; body mass index (BMI): 30. Read More

J Cell Physiol 2019 May 14;234(5):7019-7031. Epub 2018 Oct 14.

Campus UFRJ-Macaé, Universidade Federal do R io de Janeiro, Macaé, Brazil.

Obesity predisposes to glucose intolerance and type 2 diabetes (T2D). This disease is often characterized by insulin resistance, changes in insulin clearance, and β-cell dysfunction. However, studies indicate that, for T2D development, disruptions in glucagon physiology also occur. Read More

Diabetes Res Clin Pract 2018 Oct 6;144:161-170. Epub 2018 Sep 6.

Department of Endocrinology and Metabolism, Nagasaki University Hospital, Nagasaki, Japan.

Aims: To evaluate the glycaemic control of combination therapy with basal insulin and liraglutide, and to explore the factors predictive of efficacy in patients with type 2 diabetes when switched from longstanding basal-bolus insulin therapy.

Methods: We studied 41 patients who switched from basal-bolus insulin therapy of more than 3 years to basal insulin/liraglutide combination therapy. Glycaemic control was evaluated at 6 months after switching therapy and used to subdivide the patients into good-responders (HbA1c <7. Read More

Case Rep Endocrinol 2018 7;2018:6450563. Epub 2018 Aug 7.

Western Michigan University Homer Stryker M.D. School of Medicine, USA.

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are a class of medications used for glycemic control in type II diabetes mellitus. Their mechanism of action involves preventing resorption of glucose at the proximal kidney, thereby promoting glucosuria and weight loss. However, they have also been found to be associated with euglycemic diabetic ketoacidosis (euDKA). Read More

J Clin Endocrinol Metab 2018 Sep;103(9):3119-3123

University of Sydney, Sydney, New South Wales, Australia.

Context: Hyperglucagonemia in the absence of glucagonomas is rare. Biallelic-inactivating mutations in the glucagon receptor gene (GCGR) cause glucagon cell hyperplasia and neoplasia (GCHN), also termed Mahvash syndrome. Here, we report the first case to our knowledge of GCHN presenting with hypercalcemia and demonstrate a unique relationship between calcium and α-cell hyperplasia. Read More

Hepatobiliary Pancreat Dis Int 2018 Aug 8;17(4):358-362. Epub 2018 Jul 8.

Department of Endocrinology & Metabolism, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry 605006, India.

Background: Frey's procedure involves both drainage and resection of the pancreas in subjects with chronic calcific pancreatitis (CCP). The procedure may affect the pancreatic endocrine function after surgery. The present study was to evaluate the effect of Frey's procedure on both beta and alpha cell function in CCP patients. Read More

Curr Diabetes Rev 2018 06 7. Epub 2018 Jun 7.

Department of Pediatrics/Division of Pediatric Endocrinology and Metabolism, The University of Alabama at Birmingham, Birmingham, AL. United States

Background: The prevalence of type 2 diabetes (DM) in children is disturbingly increasing in parallel with increasing childhood obesity. Better knowledge regarding the pathophysiology of type 2 DM in children is paramount to devise an effective management plan.

Objective: Discuss the pathophysiology of type 2 DM in children and adolescents Methods and results: This is a comprehensive review of the literature on this topic. Read More

Cell Rep 2018 May;23(8):2532

J Clin Endocrinol Metab 2018 07;103(7):2417-2423

Division of Diabetes, Endocrinology, and Metabolism, Chiba University Hospital, Chiba, Japan.

Context: Necrolytic migratory erythema (NME) occurs in approximately 70% of patients with glucagonoma syndrome. Excessive stimulation of metabolic pathways by hyperglucagonemia, which leads to hypoaminoacidemia, contributes to NME pathogenesis. However, the molecular pathogenesis of glucagonoma and relationships between metabolic abnormalities and clinical symptoms remain unclear. Read More

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

Cell Rep 2018 02;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

Endocrinology 2018 04;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

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

Peptides 2018 02;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

Peptides 2018 02;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

J Mol Endocrinol 2018 Feb;60(2):R57-R75

Department of Surgery, BC 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

J Clin Endocrinol Metab 2018 03;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

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

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

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

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

Mol Metab 2017 10 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

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

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

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

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

Mol Cell Endocrinol 2018 01 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

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

Mol Nutr Food Res 2017 10 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

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

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

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

Arthritis Care Res (Hoboken) 2018 01 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

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

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

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

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

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

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

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

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