1. Gluconeogenesis in developing rat kidney cortex was studied by assaying the activities of two enzymes, glucose 6-phosphatase and phosphoenolpyruvate carboxykinase, and by measuring glucose formation in tissue slices. 2. Glucose 6-phosphatase and phosphoenolpyruvate carboxykinase are present in late foetal (21-22-day-old) tissue and increase rapidly postnatally. Maximum activity of phosphoenolpyruvate carboxykinase occurs at 7 days of age, followed by a decline to the adult level. Glucose 6-phosphatase activity rises during the first 2 postnatal weeks and then declines. 3. Late foetuses synthesize glucose from both pyruvate and l-glutamate. The rate increases during the first 2 weeks to above adult levels. Synthesis is always higher from pyruvate than from glutamate. 4. The effect of 24hr. starvation was studied in perinatal animals. The results indicate that the ability to increase the rate of glucose synthesis as a result of starvation is not present at birth, but develops some time after the second postnatal day.
Pancreatic and plasma insulin concentrations in preobese and lean Zucker rats were determined during three developmental periods: 1) gestation, 2) suckling, and 3) postweaning. Individual fetal samples were derived from two types of matings: 1) homozygous obese males (fafa) with heterozygous females (Fafa), and 2) homozygous lean males and females (FaFa). Suckling and postweaned pups from similar matings were partially pancreatectomized, tail bled, and identified retrospectively. In 21-day-old fetuses bearing the fa gene, plasma insulin concentration was elevated (P less than 0.001) and pancreatic concentration was slightly lower (P less than 0.05) compared to homozygous lean fetuses. Neither pancreatic nor plasma insulin concentration differed between preobese and lean pups during suckling, except that pancreatic concentration became elevated in preobese pups on postnatal day 20 (P less than 0.05). Plasma insulin concentration was elevated 24 h postweaning (P less than 0.01). These data support the hypothesis that the fa gene initiates metabolic changes during gestation that are modulated during suckling, but reappear at weaning. The data also establish that increased adipocyte size and lipoprotein lipase activity in 7- to 12-day-old preobese pups are not dependent on concomitant hyperinsulinemia.
Zucker rats were early weaned onto either medium-chain (MCT) or long-chain triglycerides (LCT) to examine the effect on the development of obesity. Preobese and lean pups were weaned at 16 days to isocaloric, isonitrogenous liquid diets containing either 65% MCT or LCT (by calories) or to a "stocklike" (5.5% fat, 72.6% carbohydrate) control diet or were pair-fed stocklike diet to MCT-fed rats until day 45. MCT-feeding lowered body weight gain and fat pad weight in obese and lean rats compared to stocklike-fed controls. Additionally, fat cell size and lipoprotein lipase (LPL) activity and hepatic acetyl CoA carboxylase activity were reduced in obese MCT-fed rats compared to obese controls fed stocklike diet. Except for altered LPL activity the effects produced by MCT-feeding were attributable to its anorectic effect. However, all obese rats, including the MCT group, developed an obese body composition and were hyperinsulinemic. The development sequence leading to obesity may be derived from a fundamental cellular defect that results in metabolic alterations in different tissues at critical periods of development. Thus, effective treatment of this genetic obesity requires a better understanding of fa gene action.
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