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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | D'Alessio, D. |
| Description | Country affiliation: United States Author Affiliation: D'Alessio D ( Department of Medicine, Division of Endocrinology, Metabolism and Diabetes, University of Cincinnati and Cincinnati VA Medical Center, Cincinnati, OH 45267-0547, USA. dalessd@ucmail.uc.edu) |
| Abstract | Excessive production of glucose by the liver contributes to fasting and postprandial hyperglycaemia, hallmarks of type 2 diabetes. A central feature of this pathologic response is insufficient hepatic insulin action, due to a combination of insulin resistance and impaired ß-cell function. However, a case can be made that glucagon also plays a role in dysregulated hepatic glucose production and abnormal glucose homeostasis. Plasma glucagon concentrations are inappropriately elevated in diabetic individuals, and -cell suppression by hyperglycaemia is blunted. Experimental evidence suggests that this contributes to greater rates of hepatic glucose production in the fasting state and attenuated reduction after meals. Recent studies in animal models indicate that reduction of glucagon action can have profound effects to mitigate hyperglycaemia even in the face of severe hypoinsulinaemia. While there are no specific treatments for diabetic patients yet available that act specifically on the glucagon signalling pathway, newer agents including glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors reduce plasma glucagon and this is thought to contribute to their action to lower blood glucose. The -cell and glucagon receptor remain tempting targets for novel diabetes treatments, but it is important to understand the magnitude of benefit new strategies would provide as preclinical models suggest that chronic interference with glucagon action could entail adverse effects as well. |
| File Format | HTM / HTML |
| ISSN | 14628902 |
| Issue Number | Suppl 1 |
| Volume Number | 13 |
| e-ISSN | 14631326 |
| Journal | Diabetes, Obesity and Metabolism |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2011-10-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Metabolism Discipline Endocrinology Discipline Pharmacology Discipline Diabetology Blood Glucose Metabolism Diabetes Mellitus, Type 2 Dipeptidyl-peptidase Iv Inhibitors Pharmacology Glucagon-like Peptide 1 Glucagon-secreting Cells Glucagon Liver Animals Diabetes Mellitus, Experimental Physiopathology Fasting Biosynthesis Blood Secretion Humans Hyperglycemia Insulin-secreting Cells Mice Journal Article Review |
| Content Type | Text |
| Resource Type | Article |
| Subject | Endocrinology, Diabetes and Metabolism Internal Medicine Endocrinology |
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