Pancreatic β-cell overexpression of the glucagon receptor gene results in enhanced β-cell function and mass
| Autor: | Heidi Sørensen, Maureen J. Charron, Jens J. Holst, Peter B. Johansen, Lingguang Cui, Raymond A. Pederson, Xiu Quan Du, Patricia Vuguin, Christopher H.S. McIntosh, Richard W. Gelling, John Rømer, Norman Fleischer, Margarita Leiser, Erica Nishimura, Christian Fledelius |
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| Rok vydání: | 2009 |
| Předmět: |
Male
endocrine system medicine.medical_specialty endocrine system diseases Physiology Endocrinology Diabetes and Metabolism medicine.medical_treatment Mice Transgenic Biology Transfection Glucagon Impaired glucose tolerance Mice Insulin resistance Insulin-Secreting Cells Physiology (medical) Internal medicine Glucose Intolerance Insulin Secretion Receptors Glucagon medicine Animals Insulin Glucose homeostasis Cells Cultured Pancreatic hormone Cell Proliferation Cell Size Glucose tolerance test medicine.diagnostic_test nutritional and metabolic diseases Articles medicine.disease Mice Inbred C57BL Endocrinology Organ Specificity Hyperglycemia Mice Inbred CBA Diet Atherogenic Female Glucagon receptor hormones hormone substitutes and hormone antagonists |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 297:E695-E707 |
| ISSN: | 1522-1555 0193-1849 |
| DOI: | 10.1152/ajpendo.00082.2009 |
| Popis: | In addition to its primary role in regulating glucose production from the liver, glucagon has many other actions, reflected by the wide tissue distribution of the glucagon receptor (Gcgr). To investigate the role of glucagon in the regulation of insulin secretion and whole body glucose homeostasis in vivo, we generated mice overexpressing the Gcgr specifically on pancreatic β-cells (RIP-Gcgr). In vivo and in vitro insulin secretion in response to glucagon and glucose was increased 1.7- to 3.9-fold in RIP-Gcgr mice compared with controls. Consistent with the observed increase in insulin release in response to glucagon and glucose, the glucose excursion resulting from both a glucagon challenge and intraperitoneal glucose tolerance test (IPGTT) was significantly reduced in RIP-Gcgr mice compared with controls. However, RIP-Gcgr mice display similar glucose responses to an insulin challenge. β-Cell mass and pancreatic insulin content were also increased (20 and 50%, respectively) in RIP-Gcgr mice compared with controls. When fed a high-fat diet (HFD), both control and RIP-Gcgr mice developed similar degrees of obesity and insulin resistance. However, the severity of both fasting hyperglycemia and impaired glucose tolerance (IGT) were reduced in RIP-Gcgr mice compared with controls. Furthermore, the insulin response of RIP-Gcgr mice to an IPGTT was twice that of controls when fed the HFD. These data indicate that increased pancreatic β-cell expression of the Gcgr increased insulin secretion, pancreatic insulin content, β-cell mass, and, when mice were fed a HFD, partially protected against hyperglycemia and IGT. |
| Databáze: | OpenAIRE |
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