Glucagon and Type 2 Diabetes: the Return of the Alpha Cell
详细信息 查看全文
- 作者：Asger Lund (1) (2)
Jonatan I. Bagger (1) (2)
Mikkel Christensen (1) (2) (3)
Filip K. Knop (1) (2)
Tina Vilsb?ll (1) - 关键词：Alpha cell ; Glucagon ; GIP ; GLP ; 1 ; Type 2 diabetes
- 刊名：Current Diabetes Reports
- 出版年：2014
- 出版时间：December 2014
- 年：2014
- 卷：14
- 期：12
- 全文大小：206 KB
- 参考文献：1. Gromada J, Franklin I, Wollheim CB. Alpha-cells of the endocrine pancreas: 35?years of research but the enigma remains. Endocr Rev. 2007;28:84-16. CrossRef
2. Unger RH, Orci L. Glucagon and the A cell: physiology and pathophysiology (first two parts). N Engl J Med. 1981;304:1518-4. CrossRef
3. Unger RH, Orci L. The essential role of glucagon in the pathogenesis of diabetes mellitus. Lancet. 1975;1:14-. CrossRef
4. Lee Y, Wang M-Y, Du XQ, Charron MJ, Unger RH. Glucagon receptor knockout prevents insulin-deficient type 1 diabetes in mice. Diabetes. 2011;60:391-. / This study shows that in the presence of glucagon deficiency, complete lack of insulin does not result in hyperglycemia—highlighting the role of glucagon on hyperglycemia. CrossRef
5. Hvidberg A, Nielsen MT, Hilsted J, ?rskov C, Holst JJ. Effect of glucagon-like peptide-1 (proglucagon 78-107 amide) on hepatic glucose production in healthy man. Metabolism. 1994;43:104-. CrossRef
6. Hare KJ, Knop FK, Asmar M, Madsbad S, Deacon CF, Holst JJ, et al. Preserved inhibitory potency of GLP-1 on glucagon secretion in type 2 diabetes mellitus. J Clin Endocrinol Metab. 2009;94:4679-7. CrossRef
7. Meier JJ, Gallwitz B, Siepmann N, Holst JJ, Deacon CF, Schmidt WE, et al. Gastric inhibitory polypeptide (GIP) dose-dependently stimulates glucagon secretion in healthy human subjects at euglycaemia. Diabetologia. 2003;46:798-01. CrossRef
8. Mitrakou A, Ryan C, Veneman T, Mokan M, Jenssen T, Kiss I, et al. Hierarchy of glycemic thresholds for counterregulatory hormone secretion, symptoms, and cerebral dysfunction. Am J Physiol. 1991;260:E67-4.
9. Rocha DM, Faloona GR, Unger RH. Glucagon-stimulating activity of 20 amino acids in dogs. J Clin Invest. 1972;51:2346-1. CrossRef
10. Ahrén B. Autonomic regulation of islet hormone secretion—implications for health and disease. Diabetologia. 2000;43:393-10. CrossRef
11. Xu E, Kumar M, Zhang Y, Ju W, Obata T, Zhang N, et al. Intra-islet insulin suppresses glucagon release via GABA-GABAA receptor system. Cell Metab. 2006;3:47-8. CrossRef
12. Luft R, Efendi? S, H?kfelt T. Somatostatin—both hormone and neurotransmitter? Diabetologia. 1978;14:1-3. CrossRef
13. De Heer J, Rasmussen C, Coy DH, Holst JJ. Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, inhibits glucagon secretion via somatostatin (receptor subtype 2) in the perfused rat pancreas. Diabetologia. 2008;51:2263-0. CrossRef
14. Gedulin BR, Rink TJ, Young AA. Dose-response for glucagonostatic effect of amylin in rats. Metabolism. 1997;46:67-0. CrossRef
15. Bagger JI, Knop FK, Lund A, Holst JJ, Vilsb?ll T. Glucagon responses to increasing oral loads of glucose and corresponding isoglycaemic intravenous glucose infusions in patients with type 2 diabetes and healthy individuals. Diabetologia. 2014. / This study describes the hyperglucagonemic response to oral glucose loads in patients with type 2 diabetes and suggests that this response may represent a pathological version of a gut-derived phenomenon.
16. Knop FK, Aaboe K, Vilsb?ll T, V?lund A, Holst JJ, Krarup T, et al. Impaired incretin effect and fasting hyperglucagonaemia characterizing type 2 diabetic subjects are early signs of dysmetabolism in obesity. Diabetes Obes Metab. 2012;14:500-0. Filip K. Knop (1) (2)
Tina Vilsb?ll (1)
1. Center for Diabetes Research, Department of Medicine, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
2. Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
3. Department of Clinical Pharmacology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark - ISSN：1539-0829
文摘
In normal physiology, glucagon from pancreatic alpha cells plays an important role in maintaining glucose homeostasis via its regulatory effect on hepatic glucose production. Patients with type 2 diabetes suffer from fasting and postprandial hyperglucagonemia, which stimulate hepatic glucose production and, thus, contribute to the hyperglycemia characterizing these patients. Although this has been known for years, research focusing on alpha cell (patho)physiology has historically been dwarfed by research on beta cells and insulin. Today the mechanisms behind type 2 diabetic hyperglucagonemia are still poorly understood. Preclinical and clinical studies have shown that the gastrointestinal hormone glucose-dependent insulinotropic polypeptide (GIP) might play an important role in this pathophysiological phenomenon. Furthermore, it has become apparent that suppression of glucagon secretion or antagonization of the glucagon receptor constitutes potentially effective treatment strategies for patients with type 2 diabetes. In this review, we focus on the regulation of glucagon secretion by the incretin hormones glucagon-like peptide-1 (GLP-1) and GIP. Furthermore, potential advantages and limitations of suppressing glucagon secretion or antagonizing the glucagon receptor, respectively, in the treatment of patients with type 2 diabetes will be discussed.