Alterations of Hepatic Enzyme Activities in KK and Yellow KK Mice with Various Diabetic States

Abstract

Hepatic enzyme activities were assayed on yellow KK and KK mice with various diabetic states. Yellow KK mice in overt diabetes showed higher activities of enzyme involving glycolysis (glucokinase and pyruvate kinase) and pentose phosphate cycle (6-phosphogluconate dehydrogenase) than KK mice in chemical diabetes between 5 and 16 weeks of age. The same trend was also noted not only on lipogenic enzymes (ATP citrate lyase, malic enzyme and acetyl-CoA carboxylase) but on gluconeogenic enzymes (glucose-6-phosphatase and fructose-1,6-diphosphatase). The observed alterations disappeared with remission of clinical entity in 52 weeks old yellow KK mice.

Nutritionally obese KK mice, fed a high calorie diet, showed hyperglycemia and hyperinsulinemia accompanying the same alteration of hepatic enzymes as that observed in yellow KK mice. Alloxan administration resulted in decreases in glycolytic enzymes in yellow KK mice to the same levels as observed in KK mice. Elevations of gluconeogenic enzyme levels due to the treatment were remarkable in KK but not in yellow KK mice, which could be accounted for by fully elevated enzyme levels in yellow KK mice before the treatment

All these data indicated that increases in the activities of the enzymes involving glycolysis, pentose phosphate cycle, lipogenesis and gluconeogenesis were associated with exaggeration of diabetes by obesity. These enzymic alterations may reflect hyperinsulinism and impairment of suppressive action by insulin on gluconeogenic enzymes.

Key words

Yellow KK Mice - KK Mice - Diabetes - Obesity - Hepatic Enzymes - Glycolysis - Lipogenesis - Pentose Phosphate Cycle - Gluconeogenesis - Insulin Action - Alloxan Diabetes - Diet