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. 1969 Oct;48(10):1878–1887. doi: 10.1172/JCI106154

Control of insulin secretion during fasting hyperglycemia in adult diabetics and in nondiabetic subjects during infusion of glucose

Charles J Goodner 1,2,3, Martin J Conway 1,2,3, Jon H Werrbach 1,2,3
PMCID: PMC322424  PMID: 5822593

Abstract

In obese adult diabetics, the concentration of insulin in venous plasma was unrelated to the degree of hyperglycemia after an overnight fast. However, in these subjects, insulin rose and fell in proportion to the magnitude of change in plasma glucose induced by small intravenous infusions of glucose. The minimal dose of glucose to cause a significant rise in insulin above the fasting level was similar in normal subjects, obese nondiabetic subjects, and in obese, hyperglycemic adult diabetics. This dose lay between infusion of 60 and 100 mg of glucose per min for 30 min. These results suggested that the secretion of insulin was under regulation by changes in blood glucose but was not stimulated in proportion to the stable raised blood glucose concentration of the hyperglycemic diabetic. Artificial hyperglycemia was induced in fasting normal subjects by constant intravenous infusion of glucose at rates of 100-250 mg of glucose per min for periods up to 8 hr. Plasma glucose rose during the 1st hr of infusion and then remained constantly elevated for up to 8 hr. The concentration of plasma insulin paralleled that of plasma glucose. During the period of constant hyperglycemia and elevated insulin, superimposition of a brief additional glucose load resulted in a prompt rise in glucose and insulin, both returning to the previous elevated levels.

Thus in normals as well as obese diabetics, stable hyperglycemia does not produce a pancreatic response sufficient to return the blood glucose to an arbitrary normal fasting concentration, yet the beta cells remain readily responsive to a change in plasma glucose. These data suggest that the beta cells do not operate as a control system with an absolute reference point when presented with systemic hyperglycemia. The behavior of the beta cells during hyperglycemia in the fasting obese adult diabetic suggests that the regulation of the basal insulin secretion may not be determined by factors directly related to the prevailing concentration of glucose. It is postulated that the beta cells adapt to hyperglycemia perhaps through the operation of controls directed toward a normal delivery of free fatty acids or some other cellular metabolic substrate during fasting.

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Selected References

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