Both glucagon and glucagon-like peptide-1 (GLP-1) play an important role in the regulation of nutrient homeostasis. In this study, the tissue distributions of the expression of receptor genes for glucagon and GLP-1 were examined. Expression of glucagon receptor gene was detected in liver, kidney, ileum and pancreatic islets but not in brain. In contrast, expression of GLP-1 receptor gene was detected in brain, pancreas and pancreatic islets but not in liver, kidney, or ileum. To investigate the existence and characteristics of glucagon and GLP-1 receptors on pancreatic beta cells, expression of the receptor genes and translational regulation of the expression of the receptor genes by glucose were analyzed in a mouse pancreatic beta cell line, MIN6 cells. In the cDNA pool of MIN6 cells, both glucagon and GLP-1 receptor genes were identified and showed higher expression level in MIN6 cells cultured under high glucose condition than in those cultured under low glucose condition. These results suggest that glucagon and GLP-1 receptor genes are expressed in pancreatic beta cells and their expression is upregulated by glucose.
An obese 68-year-old woman was admitted for examination of fasting hypoglycaemia. A prolonged 18 h fast reduced her plasma glucose without suppressing insulin secretion, while plasma β-hydroxybutyrate levels were suppressed. Despite the prolonged fast, the glucose response to glucagon was increased by 25 mg/dL (1.39 mM) glucose, which is compatible with insulinoma. A 75 g oral glucose tolerance test (75 g OGTT) showed impaired glucose tolerance. An abdominal CT scan revealed a mass lesion in the uncinate process of the pancreas, a finding consistent with the results of angiography and selective artery calcium injection test. The patient then underwent a pancreaticoduodenectomy; the pancreatic mass was histologically diagnosed as benign insulinoma. After surgery, a prolonged 24 h fast caused no hypoglycaemia and the glucose tolerance capacity in 75 g OGTT improved. Eight months after surgery, the patient's body weight had reduced by 10 kg. This is therefore a case of concurrent insulinoma and impaired glucose tolerance.
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