Summary
The effect of exogenous insulin on glucagon release by guinea pig A2-cells of isolated islets from normal and streptozotocin treated animals has been studied to test the hypothesis that insulin directly affects glucagon secretion. Glucose utilization and ATP concentration were also measured. In addition, the effects of exogenous somatostatin on glucagon release and glucose utilization of these cells have been investigated. In the A2-cell rich islets from streptozotocin treated guinea pigs glucagon release was 76.9±7.8 pg/μg islet dry weight/h in 1.7 mmol/l glucose, not being significantly inhibited when the glucose concentration was increased up to 16.7 mmol/l. Glucagon release was, however, strongly suppressed by 30 mU/ml insulin independent of the glucose concentration, while release from the normal islets was unaffected by exogenous insulin. Glucose utilization increased four-fold in the A2cell rich islets when the glucose level was raised from 1.7 to 16.7 mmol/l, but was nevertheless at all times less than 70 per cent of that of the normal islets. Addition of exogenous insulin caused a further significant stimulation (40–100 per cent) in the A2-cell rich islets, but not in the normal islets. The ATP concentration of the A2-cell rich islets increased in parallel with the glucose concentration. Addition of insulin effected the highest ATP levels, about 15 mmol/kg islet dry weight, irrespective of the glucose concentration. Somatostatin (2.5 μg/ml) strongly inhibited glucagon release, but failed to affect glucose utilization. The present observations support the view that the A2-cell is sensitive to insulin, and suggest that the suppressive effect of insulin on glucagon release is mediated via an increased intracellular ATP concentration generated by stimulated glucose metabolism.
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This work was supported by grants from the Swedish Medical Research Council (B79-12X-001-15B and B79-12X-0229712C), the Swedish Diabetes Association, the Medical Faculty of the University of Uppsala and the Swedish Society for Medical Research.
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Östenson, C.G. Regulation of glucagon release: Effects of insulin on the pancreatic A2-cell of the guinea pig. Diabetologia 17, 325–330 (1979). https://doi.org/10.1007/BF01235889
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DOI: https://doi.org/10.1007/BF01235889