Acute disruption of glucagon secretion or action does not improve glucose tolerance in an insulin-deficient mouse model of diabetes

Diabetologia

Volumn 59, Issue 2, 2016, Pages 363-370

  Steenberg, Vivi R ^a   Jensen, Signe M ^a   Pedersen, Jens ^a   Madsen, Andreas N ^a   Windeløv, Johanne A ^a   Holst, Birgitte ^a   Quistorff, Bjørn ^a   Poulsen, Steen S ^a   Holst, Jens J ^a  

^a Capital Region   (Denmark)

Author keywords

Endocrine pancreas; Glucagon; Glucose homeostasis; Streptozotocin; Type 1 diabetes

Indexed keywords

DIPHTHERIA TOXIN; DIPHTHERIA TOXIN RECEPTOR; GLUCAGON; GLUCAGON ANTIBODY; GLUCAGON LIKE PEPTIDE 1; GLUCAGON RECEPTOR; GLUCAGON RECEPTOR ANTAGONIST; GLUCOSE; GLYCOGEN; KETONE; LACTIC ACID; PROGLUCAGON; RECEPTOR; STREPTOZOCIN; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; GLUCOSE BLOOD LEVEL; INSULIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIBODY AFFINITY; ARTICLE; BODY WEIGHT; CONTROLLED STUDY; DISEASE SEVERITY; GLUCAGON BLOOD LEVEL; GLUCAGON RELEASE; GLUCONEOGENESIS; GLUCOSE BLOOD LEVEL; GLUCOSE TOLERANCE; GLYCOGEN ANALYSIS; MALE; MOUSE; MOUSE MODEL; NONHUMAN; ORAL GLUCOSE TOLERANCE TEST; PANCREAS ISLET ALPHA CELL; PRIORITY JOURNAL; STREPTOZOTOCIN-INDUCED DIABETES MELLITUS; TRANSGENIC MOUSE; TRIACYLGLYCEROL BLOOD LEVEL; WILD TYPE; ANIMAL; ANTAGONISTS AND INHIBITORS; BLOOD; C57BL MOUSE; CHEMICALLY INDUCED; DEFICIENCY; DRUG EFFECTS; EXPERIMENTAL DIABETES MELLITUS; GENETICS; GLUCOSE INTOLERANCE; GLUCOSE TOLERANCE TEST; KNOCKOUT MOUSE; METABOLISM; PANCREAS ISLET BETA CELL; PATHOLOGY; PHYSIOLOGY; SECRETION (PROCESS);

ANIMALS; BLOOD GLUCOSE; DIABETES MELLITUS, EXPERIMENTAL; DIPHTHERIA TOXIN; GLUCAGON; GLUCAGON-LIKE PEPTIDE 1; GLUCAGON-SECRETING CELLS; GLUCOSE INTOLERANCE; GLUCOSE TOLERANCE TEST; INSULIN; INSULIN-SECRETING CELLS; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; RECEPTORS, GLUCAGON; STREPTOZOCIN;

EID: 84953351080     PISSN: 0012186X     EISSN: 14320428     Source Type: Journal    
DOI: 10.1007/s00125-015-3794-2     Document Type: Article

References (23)

1. Banting FG, Best CH, Collip JB, Campbell WR, Fletcher AA (1922) Pancreatic extracts in the treatment of diabetes mellitus. Can Med Assoc J 12:141–146
2. Unger RH, Orci L (1975) The essential role of glucagon in the pathogenesis of diabetes mellitus. Lancet 1:14–16
3. Gelling RW, Du XQ, Dichmann DS et al (2003) Lower blood glucose, hyperglucagonemia, and pancreatic alpha cell hyperplasia in glucagon receptor knockout mice. Proc Natl Acad Sci U S A 100:1438–1443
4. Lee Y, Wang MY, Du XQ, Charron MJ, Unger RH (2011) Glucagon receptor knockout prevents insulin-deficient type 1 diabetes in mice. Diabetes 60:391–397
5. Lee Y, Berglund ED, Wang MY et al (2012) Metabolic manifestations of insulin deficiency do not occur without glucagon action. Proc Natl Acad Sci U S A 109:14972–14976
6. Thorel F, Damond N, Chera S et al (2011) Normal glucagon signaling and β-cell function after near-total α-cell ablation in adult mice. Diabetes 60:2872–2882
7. Pedersen J, Ugleholdt RK, Jorgensen SM et al (2013) Glucose metabolism is altered after loss of L cells and alpha-cells but not influenced by loss of K cells. Am J Physiol Endocrinol Metab 304:E60–E73
8. Sorensen H, Brand CL, Neschen S et al (2006) Immunoneutralization of endogenous glucagon reduces hepatic glucose output and improves long-term glycemic control in diabetic ob/ob mice. Diabetes 55:2843–2848
9. Kodra JT, Jorgensen AS, Andersen B et al (2008) Novel glucagon receptor antagonists with improved selectivity over the glucose-dependent insulinotropic polypeptide receptor. J Med Chem 51:5387–5396
10. Holst JJ (1980) Evidence that glicentin contains the entire sequence of glucagon. Biochem J 187:337–343
11. Orskov C, Rabenhoj L, Wettergren A, Kofod H, Holst JJ (1994) Tissue and plasma concentrations of amidated and glycine-extended glucagon-like peptide I in humans. Diabetes 43:535–539
12. Brand CL, Jorgensen PN, Knigge U et al (1995) Role of glucagon in maintenance of euglycemia in fed and fasted rats. Am J Physiol 269:E469–E477
13. Katz J, Golden S, Wals PA (1976) Stimulation of hepatic glycogen synthesis by amino acids. Proc Natl Acad Sci U S A 73:3433–3437
14. Holst JJ (2007) The physiology of glucagon-like peptide 1. Physiol Rev 87:1409–1439
15. Baggio LL, Drucker DJ (2007) Biology of incretins: GLP-1 and GIP. Gastroenterology 132:2131–2157
16. Kelly RP, Garhyan P, Raddad E et al (2015) Short-term administration of the glucagon receptor antagonist LY2409021 lowers blood glucose in healthy people and in those with type 2 diabetes. Diabetes Obes Metab 17:414–422
17. Brand CL, Rolin B, Jorgensen PN, Svendsen I, Kristensen JS, Holst JJ (1994) Immunoneutralization of endogenous glucagon with monoclonal glucagon antibody normalizes hyperglycaemia in moderately streptozotocin-diabetic rats. Diabetologia 37:985–993
18. Hayashi Y (2011) Metabolic impact of glucagon deficiency. Diabetes Obes Metab 13(Suppl 1):151–157
19. Omar BA, Andersen B, Hald J, Raun K, Nishimura E, Ahren B (2014) Fibroblast growth factor 21 (FGF21) and glucagon-like peptide 1 contribute to diabetes resistance in glucagon receptor-deficient mice. Diabetes 63:101–110
20. Ali S, Lamont BJ, Charron MJ, Drucker DJ (2011) Dual elimination of the glucagon and GLP-1 receptors in mice reveals plasticity in the incretin axis. J Clin Invest 121:1917–1929
21. Wang MY, Yan H, Shi Z et al (2015) Glucagon receptor antibody completely suppresses type 1 diabetes phenotype without insulin by disrupting a novel diabetogenic pathway. Proc Natl Acad Sci U S A 112:2503–2508
22. Baldissera FG, Holst JJ, Knuhtsen S, Hilsted L, Nielsen OV (1988) Oxyntomodulin (glicentin-(33-69)): pharmacokinetics, binding to liver cell membranes, effects on isolated perfused pig pancreas, and secretion from isolated perfused lower small intestine of pigs. Regul Pept 21:151–166
23. Seghieri M, Rebelos E, Gastaldelli A et al (2013) Direct effect of GLP-1 infusion on endogenous glucose production in humans. Diabetologia 56:156–161