Defects in liver and muscle glycogen metabolism in neonatal and adult New Zealand obese mice.
Impaired glycogen synthesis is present in subjects at risk for developing non-insulin-dependent diabetes mellitus (NIDDM), suggesting that it 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-old insulin-resistant New Zealand Obese (NZO) mice and control (NZC) mice. In livers of both neonatal and adult NZO mice, active GS was reduced 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% higher 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 weeks of age. Active and total GP were the same in NZO and NZC animals, despite hyperinsulinemia in 20-week-old NZO mice. In muscle, active GS was reduced by 41% in both 1-day- and 20-week-old NZO mice (P < .02). Total GS was also lower in NZC mice at 1 day of age (P < .01), but not at 20 weeks. No differences were detected in GP activity or in total glycogen content in muscle. Therefore, reduced GS activity is an early defect present at birth in the insulin-resistant NZO mouse in both liver and muscle. However, it is not the sole determinant of the amount of glycogen deposited in tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006003:Glycogen / Q000032:analysis / Q000378:metabolism*; D006006:Glycogen Synthase / Q000032:analysis; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008112:Liver Glycogen / Q000032:analysis / Q000378:metabolism; D008297:Male; D051379:Mice; D008820:Mice, Obese / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism*; D006005:Phosphorylases / Q000032:analysis
D001786:Blood Glucose; D008112:Liver Glycogen; D006003:Glycogen; D006005:Phosphorylases; D006006:Glycogen Synthase