Studies on Diabetogenic Action of Obesity in Mice

Congenital Insulin Resistance of KK Mice

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Inheritance of insulin sensitivity has been studied on C57BL, KK and their F₁-hybrids with or without the yellow obese gene (A^y).
Intraperitoneal injection of insulin was followed by a remarkable fall of the blood glucose in C57BL, but a slight fall in KK. In vitro, the adipose tissue of C57BL showed more remarkable response to insulin in glucose-1-¹⁴C oxidation than that of KK. F₁-hybrid clearly showed intermediate sensitivity to the hormone between the parental strains both in vivo and in vitro.
The yellow hybrid, A^y (the yellow obese gene)-carrying F₁-hybrid, showed adiposity and hyperinsulinemia, but did not develop the diabetic symptoms observed in yellow KK, A^y-carrying KK, such as hyperglycemia and degranulation of pancreatic B cells. In the hormone sensitivity of adipose tissue, yellow hybrid was less sensitive than nonyellow hybrid, but more sensitive than KK or yellow KK.
These data suggest that the insulin resistance of KK may be determined by a dosage of polygenes, and may result in higher susceptibility to diabetogenic action of the obesity caused by A^y gene.