Synergistic effects of male sex and obesity on hepatic insulin dynamics in SHR/Mcc-cp rat

Magda M I Hennes, Sylvia A. McCune, Earl Shrago, Ahmed H. Kissebah

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Abstract

The effects of obesity and sex on hepatic insulin metabolism were evaluated in the SHR/Mcc-cp rat. During in situ liver perfusion, insulin clearance rate (CLR) expressed per gram of liver tissue was reduced by 58 and 68% in obese females and males, respectively, compared with lean controls. Male sex resulted in CLR reductions of 46% in lean and 59% in obese animals. Obesity resulted in 50% reduction of insulin-receptor binding to isolated hepatocytes. In both lean and obese animals, male sex also resulted in a decrease of ∼34% in insulin binding. Scatchard plots indicated that the reduction in insulin binding was primarily due to a decrease in number of cell surface receptors. Receptor-mediated insulin degradation was 40% less in obese than lean animals. Male sex also resulted in 27% less insulin degradation relative to females. Receptor-mediated insulin partitioning between four compartments (cell surface bound, internalized and/or cryptic, degraded, and dissociated or released intact), expressed as a percentage of the initial membrane-bound hormone, did not differ between the animal groups. Thus, male sex and obesity are independently and additively associated with a reduction in hepatic insulin clearance and a decrease in the number of cell surface insulin receptors with a proportional decrease in insulin compartmentalization and degradation. This mechanism may partly account for the synergistic effects of male sex and obesity on the degree of hyperinsulinemia and insulin resistance and the predisposition to diabetes.

Original languageEnglish (US)
Pages (from-to)789-795
Number of pages7
JournalDiabetes
Volume39
Issue number7
StatePublished - Jul 1990

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Obesity
Insulin
Insulin Receptor
Liver
Cell Surface Receptors
Hyperinsulinism
Insulin Resistance
Hepatocytes
Perfusion
Hormones
Membranes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Synergistic effects of male sex and obesity on hepatic insulin dynamics in SHR/Mcc-cp rat. / Hennes, Magda M I; McCune, Sylvia A.; Shrago, Earl; Kissebah, Ahmed H.

In: Diabetes, Vol. 39, No. 7, 07.1990, p. 789-795.

Research output: Contribution to journalArticle

Hennes, MMI, McCune, SA, Shrago, E & Kissebah, AH 1990, 'Synergistic effects of male sex and obesity on hepatic insulin dynamics in SHR/Mcc-cp rat', Diabetes, vol. 39, no. 7, pp. 789-795.
Hennes, Magda M I ; McCune, Sylvia A. ; Shrago, Earl ; Kissebah, Ahmed H. / Synergistic effects of male sex and obesity on hepatic insulin dynamics in SHR/Mcc-cp rat. In: Diabetes. 1990 ; Vol. 39, No. 7. pp. 789-795.
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abstract = "The effects of obesity and sex on hepatic insulin metabolism were evaluated in the SHR/Mcc-cp rat. During in situ liver perfusion, insulin clearance rate (CLR) expressed per gram of liver tissue was reduced by 58 and 68{\%} in obese females and males, respectively, compared with lean controls. Male sex resulted in CLR reductions of 46{\%} in lean and 59{\%} in obese animals. Obesity resulted in 50{\%} reduction of insulin-receptor binding to isolated hepatocytes. In both lean and obese animals, male sex also resulted in a decrease of ∼34{\%} in insulin binding. Scatchard plots indicated that the reduction in insulin binding was primarily due to a decrease in number of cell surface receptors. Receptor-mediated insulin degradation was 40{\%} less in obese than lean animals. Male sex also resulted in 27{\%} less insulin degradation relative to females. Receptor-mediated insulin partitioning between four compartments (cell surface bound, internalized and/or cryptic, degraded, and dissociated or released intact), expressed as a percentage of the initial membrane-bound hormone, did not differ between the animal groups. Thus, male sex and obesity are independently and additively associated with a reduction in hepatic insulin clearance and a decrease in the number of cell surface insulin receptors with a proportional decrease in insulin compartmentalization and degradation. This mechanism may partly account for the synergistic effects of male sex and obesity on the degree of hyperinsulinemia and insulin resistance and the predisposition to diabetes.",
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