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EJE PRIZE 2018: A gut feeling about glucagon

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  4. Safety and convenience of once-weekly somapacitan in adult GH deficiency: a 26-week randomized, controlled trial

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  5. Genetic influence on the associations between IGF-I and glucose metabolism in a cohort of elderly twins

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  1. Investigating Intestinal Glucagon after Roux-en-Y Gastric Bypass Surgery

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  2. The Effect of Different Training Intensities on Oxidatively Generated Modifications of Nucleic Acids: A Randomized, Controlled Trial

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  3. Non-alcoholic fatty liver disease alters expression of genes governing hepatic nitrogen conversion

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  4. The Liver-α-Cell Axis and Type 2 Diabetes

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  5. Evaluation of clinical translatability of the diet-induced obese and biopsy-confirmed gubra amylin mouse model of non-alcoholic steatohepatitis

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Hyperglucagonaemia (in the fasting as well as in the postprandial state) is considered a core pathophysiological component of diabetes and is found to contribute substantially to the hyperglycaemic state of diabetes. Hyperglucagonaemia is usually viewed upon as a consequence of pancreatic alpha cell insensitivity to the glucagon-suppressive effects of glucose and insulin. Since we observed that the well-known hyperglucagonaemic response to oral glucose in patients with type 2 diabetes is exchanged by normal suppression of plasma glucagon levels following isoglycaemic intravenous glucose administration in these patients, we have been focusing on the gut and gut-derived factors as potential mediators of diabetic hyperglucagonaemia. In a series of clinical experiments, we have elucidated the role of gut-derived factors in diabetic hyperglucagonaemia and shown that glucose-dependent insulinotropic polypeptide promotes hyperglucagonaemia and that glucagon, hitherto considered a pancreas-specific hormone, may also be secreted from extrapancreatic tissues - most likely from proglucagon-producing enteroendocrine cells. Furthermore, our observation that fasting hyperglucagonaemia is unrelated to the diabetic state, but strongly correlates with obesity, liver fat content and circulating amino acids, has made us question the common 'pancreacentric' and 'glucocentric' understanding of hyperglucagonaemia and led to the hypothesis that steatosis-induced hepatic glucagon resistance (and reduced amino acid turnover) and compensatory glucagon secretion mediated by increased circulating amino acids constitute a complete endocrine feedback system: the liver-alpha cell axis. This article summarises the physiological regulation of glucagon secretion in humans and considers new findings suggesting that the liver and the gut play key roles in determining fasting and postabsorptive circulating glucagon levels.

Original languageEnglish
JournalEuropean Journal of Endocrinology
Volume178
Issue number6
Pages (from-to)R267-R280
ISSN0804-4643
DOIs
Publication statusPublished - Jun 2018

    Research areas

  • Diabetes Mellitus, Type 2/blood, Enteroendocrine Cells/metabolism, Fasting, Fatty Liver, Gastrointestinal Tract/physiopathology, Glucagon/blood, Glucagon-Secreting Cells/physiology, Glucose/administration & dosage, Glucose Tolerance Test, Humans, Hyperglycemia, Liver/physiopathology, Proglucagon/biosynthesis

ID: 55791425