In obese patients with noninsulin-dependent diabetes mellitus (NIDDM), reducing calorie intake improves glycemic control, often more rapidly than weight loss. Conversely, after weight loss has been achieved, metabolic control can deteriorate once calorie intake is increased, even if there is no regaining of weight. The current study, therefore, tested the hypothesis that restricting calorie consumption has an important role, independent of weight loss, in metabolic regulation of NIDDM patients. Isotopic determinations of hepatic glucose production (HGP), post-absorptively and after ingestion of 75 g glucose (dual glucose isotope method), were made in conjunction with measurement of insulin secretion and insulin sensitivity in seven obese NIDDM volunteers after four periods of controlled calorie intake: 1) 7 days of a baseline weight maintenance diet, 2) followed immediately by 7 days of calorie restriction (800 Cal/day); 3) followed by a weight loss program that consisted of 2 months of a very low calorie diet (400 Cal/day) and then 4 weeks of gradual refeeding and 7 days on a weight maintenance diet; and 4) a final week of calorie restriction (800 Cal/day). The initial brief interval of calorie restriction produced substantial decreases in fasting plasma glucose, HGP, and fasting plasma triglyceride and increases in insulin sensitivity and secretion. After a substantial weight loss (12.7 +/- 2 kg), each parameter improved further, with the effect of weight loss approximately equal to that obtained with initial calorie restriction. Reimposing calorie restriction after weight loss had little effect, except that fasting plasma glucose and HGP improved slightly further. In obese NIDDM subjects, a 7-day period of calorie restriction produces approximately half of the overall improvement in HGP, insulin sensitivity, and insulin secretion that is obtained after a substantial loss of weight. These findings indicate that calorie restriction has an important regulatory effect on the metabolism of obese patients with NIDDM that is independent of weight loss.

Immature female rats received implants containing 17 beta-estradiol on postnatal day 28 at 0900 h, followed 24 h later by either blank capsules or progesterone. Between 1500-1600 h on the day of progesterone (or blank capsule) implantation, these rats, a group of unoperated or sham controls, and a group of estrogen-progesterone-treated immature male rats were killed and perfused, and their brains processed for immunocytochemistry of c-fos antigen and LHRH. LHRH neurons consistently expressed c-fos after estrogen-progesterone treatment in females but not males; in only one of four females examined was c-fos induced after estrogen treatment. No fos was associated with LHRH neurons in the control groups. The LHRH neurons that expressed c-fos were located in the preoptic area and anterior hypothalamus; more rostral LHRH cells did not appear stimulated. These data demonstrate that gonadal steroids, administered in a paradigm that predictably produces timed stimulation of LH release, induce c-fos in LHRH neurons. The induction of c-fos in LHRH neurons provides a potentially useful and powerful tool for studying LHRH activation at the cellular level.

No abstract

The c-fos protein is rapidly induced in hypothalamic magnocellular nuclei following hemorrhage. We used specific antibodies directed against c-fos and either vasopressin (AVP) or oxytocin (OT) neurophysin to investigate c-fos activation in individual AVP and OT neurons. AVP and OT neurons expressed c-fos in response to hypovolemic stimuli. Following a protocol of incremental hemorrhage, AVP and OT neurons expressed c-fos with a graded response that correlated with stimulus intensity. As the volume of hemorrhage increased, there was an increase in the number of cells expressing c-fos as well as in the amount of c-fos immunoreactivity per cell. These increases correlated with the amount of hormone released into the peripheral blood. In addition, a differential pattern of activation for AVP neurons occurred in response to hemorrhagic stimuli. AVP neurons in the supraoptic nucleus (SON) had a lower threshold for response than those in the paraventricular nucleus (PVN). For OT, activation required a greater blood loss than AVP and c-fos expression encompassed both SON and PVN neurons. We conclude that c-fos expression is proportional to stimulus intensity and reveals functional heterogeneity among magnocellular neurons.