Regulation of glucagon gene expression by insulin

To study the effects of 10e-6 and 10e-7 M exogenous insulin [the concentrations which correspond to insulin concentrations in core capillaries of islets in-vivo] on glucagon gene regulation in intact islets in RPMI 1640 culture medium. Design: An experimental study. Place and Duration of Study: The study was carried out in the Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi and the Department of Metabolic Medicine, Hammersmith Hospital, London from 1995 to 1996. Subjects and Wistar rats were used to obtain visible islets from pancreas by collagenase degradation of exocrine tissue. The effect of 10-s and 10- M insulin was observed on glucagon and insulin mRNA and glucagon, Insulin and somatostatin secretions in the culture medium at the end of 18 hours of incubation. Insulin decreased glucagon levels in culture medium [366.7 +/- 42.9 in 10e-6 M insulin vs 450 +/- 38.9 in controls; p < 0.01]. No significant effect on glucagon secretion by 10-7 M insulin was observed. Reduction of glucagon mRNA by insulin was also observed [77.8 +/- 30.3 in 10e-6 and 94.5 +/- 15.6% control in 10e-7 M insulin]. Somatostatin secretions decreased in culture medium by 10e-6 and 10e-7 M insulin as compared to controls [103.6 +/- 16.4 in 10e-6 M insulin and 115.4 +/- 7.4 in 10e-7 M insulin vs 166.6 +/- 19.9 in control islets, p <0.001]. Insulin mRNA was inhibited by insulin [91.5 +/- 35.4 in 10e-6 M insulin and 94.8 +/- 19% controls in 10e-7 M insulin]. Concentrations of insulin were significantly high as compared to controls in medium of islets treated with 10e-6 M insulin [107876 +/- 5837 in 10e-6 M insulin vs 57205 +/- 8392 in control islets, p <0.001]. No significant difference in insulin levels in medium existed in 10e-7 M insulin as compared to control islets. It is concluded that insulin normalizes hyperglucagonemia in diabetics by exerting its effects at gene transcription level and somatostatin is negatively regulated by insulin