DEFECTS IN LIVER AND MUSCLE GLYCOGEN-METABOLISM IN NEONATAL AND ADULTNEW-ZEALAND OBESE MICE

Impaired glycogen synthesis is present in subjects at risk for develop ing non-insulin-dependent diabetes mellitus (NIDDM), suggesting that i t is a primary defect in NIDDM. To examine whether defects in glycogen metabolism are present at birth in an animal model of NIDDM glycogen synthase (GS), glycogen phosphorylase (GP), and total glycogen content were measured in liver and quadriceps muscle of 1-day- and 20-week-ol d insulin-resistant New Zealand Obese (NZO) mice and control (NZC) mic e. In livers of both neonatal and adult NZO mice, active GS was reduce d by 54% and 36%, respectively, as compared with that in NZC mice (P<. 03). Total liver GS activity was the same in neonates, but was 65% hig her in adult NZO as compared with NZC mice (P<.02). Liver glycogen was 28% lower at birth in NZO mice (P<.03), but was 49% higher at 20 week s of age. Active and total GP were the same in NZO and NZC animals, de spite hyperinsulinemia in 20-week-old NZO mice. In muscle, active GS w as reduced by 41% in both 1-day- and 20 week-old NZO mice (P<.02). Tot al GS was also lower in NZC mice at 1 day of age (P<.01), but not at 2 0 weeks. No differences were detected in GP activity or in total glyco gen content in muscle. Therefore, reduced GS activity is an early defe ct present at birth in the insulin-resistant NZO mouse in both liver a nd muscle. However, it is not the sole determinant of the amount of gl ycogen deposited in tissues. Elevated liver glycogen in adult NZO mice may contribute to hepatic glucose overproduction. Copyright (C) 1995 by W.B. Saunders Company