Feedback Inhibition of Insulin Secretion by Insulin: Relation to the Hyperinsulinemia of Obesity

D. Elahi, M. Nagulesparan, R. J. Hershcopf, D. C. Muller, J. D. Tobin, P. M. Blix, A. H. Rubenstein, Roger H Unger, R. Andres

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200 Scopus citations


We investigated the possible existence of a negative short-loop feedback of circulating insulin on the parent beta cell in 10 lean Caucasians, 10 obese Caucasians, and 10 obese Pima Indians. Plasma insulin levels were raised acutely by 100 μU per milliliter for 90 minutes, and plasma glucose was maintained by the“clamp”technique. C-peptide levels were suppressed in all groups to approximately 50 per cent of basal values. However, the obese groups had absolute C-peptide levels much higher than those of the lean group. During the hour after infusion, the rate and magnitude of C-peptide recovery in the obese groups were higher than in the lean group. Thus, negative short-loop insulin-beta-cell feedback was operative in both the lean and obese states. Despite this suppression, the insulin-secretion rate in obese subjects was still greater than that in non-obese subjects. Inadequate feedback suppression may account in part for the prevailing hyperinsulinemia of the obese. (N Engl J Med. 1982; 306:1196–1202.) OBESITY in both human beings and rodents is associated with hyperinsulinemia. Insulin levels are elevated not only in the basal state but also under conditions that stimulate insulin secretion. The mechanism underlying this hyperinsulinemia is not known. The circulating insulin level is a result of the rate of insulin secretion and of its metabolic clearance rate. Secretion is in turn influenced by a complex of stimulatory and inhibitory influences on the beta cell. Among the inhibitory influences is the still-controversial possibility of a direct or indirect negative feedback of circulating insulin on beta-cell secretion. There is evidence both for1 2 3 4 5 6 7 8 9 10 11 12 13 and. . .

Original languageEnglish (US)
Pages (from-to)1196-1202
Number of pages7
JournalNew England Journal of Medicine
Issue number20
StatePublished - May 20 1982

ASJC Scopus subject areas

  • Medicine(all)


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