The diabetogenic effects of streptozotocin (STZ) (40 or 60 mg /kg body wt, i.v.) were examined in rats that had been previously fed either a high-protein, carbohydrate-free (HP) diet (70% protein, 8% fat) or a control diet (66% carbohydrate, 16% protein, 8% fat), and maintained on the same diets after drug injection. Rats on the HP diet 15–21 days before STZ administration showed reduced mortality and decreased severity of diabetes as judged by rate of body-weight change, plasma glucose, urine volume and glycosuria, serum and pancreatic insulin, and morphology of islets of Langerhans. In rats on the control diet, values for serum and pancreatic insulin did not differ 2 and 14 days after 40 mg/kg of STZ. In contrast, in rats under the HP regimen, serum insulin levels doubled 14 days after STZ and pancreatic insulin content was almost 20 times higher than at day 2. Rats previously fed on the HP diet for 21 days, but transferred to the control diet 2 days after STZ injection, also showed reduced severity of diabetes, as indicated by rates of body-weight gain, urinary excretion of urea, and levels of serum and pancreatic insulin. However, in these animals the effects of the HP diet were not as marked as those observed in the rats that were maintained on the HP diet after STZ injection. These findings indicate that the rapid amelioration of diabetes in rats adapted to the HP diet results from the combination of two beneficial effects of the diet: (1) an initial partial protection against the diabetogenic activity of the drug at the time of exposure, and (2) a subsequent improvement of the induced diabetic state. The data suggest that adaptation of rats to a high-protein diet entails a decreased susceptibility of the beta cells to the cytotoxic action of STZ and an enhancement of the restorative capacity Of these cells.
Previous studies indicated that a longitudinal pathway connecting preoptic, lateral, and posterior hypothalamic areas participates in the process of free fatty acid (FFA) mobilization in the rat. In the present experiments, the presence of sensitive neurons in the preoptic area was investigated by examining the effects of topical stimulation with 2-deoxyglucose (2-DG) or insulin on the levels of plasma FFA in conscious unrestrained rats. Microinjections of minute amounts (50 micrograms and 1 microliter) of 2-DG into the preoptic area of fed animals induced rapid increases in the concentration of plasma FFA. Microinjections of insulin (5 microU and 0.5 microliter) produced sharp decreases of the elevated plasma FFA levels in fasted rats. Both 2-DG and insulin induced small increases in plasma glucose that did not differ from similar increases induced by equal volumes of 0.15 M NaCl. The results provide direct evidence for the presence within the preoptic area of insulin-sensitive glucoreceptors involved in FFA mobilization. The data suggest that activation of these receptors and increased sympathetic outflow to adipose tissue contributes to fasting lipolysis.
During the 24-hr period after 70% hepatectomy, rats kept without food were found to maintain blood glucose levels comparable to those of sham-operated controls. As indicated by measurements of L-alanine-14C and H14CO3 incorporation into glucose and net glucose production, the rate of gluconeogenesis in liver slices was higher for the partially hepatectomized rats than for sham-operated controls. The enhanced gluconeogenesis exhibited by the residual tissue from the hepatectomized animals was not accompanied by increase in the activity of either glucose-6-phosphatase and fructose-1, 6-diphosphatase.
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