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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1985 Mar;82(5):1544–1546. doi: 10.1073/pnas.82.5.1544

Correction of hyperglycemia with phloridzin restores the glucagon response to glucose in insulin-deficient dogs: implications for human diabetes.

A Starke, S Grundy, J D McGarry, R H Unger
PMCID: PMC397300  PMID: 3883362

Abstract

In insulin-deprived alloxan-induced diabetic dogs with severe hyperglycemia and marked hyperglucagonemia, glucagon was not suppressed by intravenous infusion of glucose at a progressively increasing rate up to 24 mg/kg of body weight per min. However, when the hyperglycemia was corrected by phloridzin, a blocker of renal tubular glucose reabsorption, the hyperglucagonemia was readily suppressed by as little as 2 mg of glucose per kg/min. Direct perfusion of phloridzin into the isolated pancreas of nondiabetic dogs had no effect on the in vitro glucagon response to increments in glucose. However, in pancreata isolated from dogs whose glucose levels had been lowered by phloridzin pretreatment, in vitro glucagon suppression in response to glucose increments was more than twice that of controls. This enhancing effect of phloridzin treatment was completely abolished by giving an intravenous infusion of glucose for the 5 hr prior to surgery for isolation of the pancreas. It is concluded that (i) alpha cells have a glucose-sensing system that is independent of insulin and beta cells, and (ii) this system is reversibly attenuated by hyperglycemia. Thus, hyperglycemia, a metabolic consequence of islet cell dysfunction, may be a self-exacerbating inducer of further islet cell dysfunction, a possibility with implications for human diabetes.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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