Yutaro Takamura

Very-Low-Calorie Diet-Induced Weight Reduction Reverses Impaired Growth Hormone Secretion Response to Growth Hormone-Releasing Hormone, Arginine, and L-Dopa in Obesity

To determine whether impaired growth hormone (GH) secretion in obese subjects is a consequence of obesity or a pre-existing pituitary-hypothalamic disorder, we measured (1) plasma GH response to growth hormone-releasing hormone (GRH; 1 microgram/kg body weight [BW]), arginine (0.5 g/kg BW), and L-dopa (500 mg); and (2) plasma glucose, insulin, and free fatty acids (FFA) in obese subjects before and after weight reduction due to very-low-calorie diet therapy using Optifast (240 kcal/d for 8 to 12 weeks). Body weight and body mass index (BMI) values before and after weight reduction were 87.2 +/- 4.1 kg and 34.5 +/- 0.9 kg/m2, and 67.8 +/- 2.7 kg and 27.0 +/- 0.4 kg/m2, respectively. GH response to GRH, arginine, and L-dopa in obese subjects was markedly impaired before weight reduction, whereas significantly increased responses were noted after weight reduction (P less than .01). Impaired integrated GH response to GRH, arginine, and L-dopa in obese subjects was significantly restored after weight reduction (P less than .01). Plasma glucose levels did not change, while plasma insulin and FFA levels decreased significantly after weight reduction (P less than .01, P less than .05). There was no significant correlation between integrated GH response to these three stimuli and plasma levels of glucose, insulin, and FFA, respectively. The reversibility of GH response to all three stimuli after weight reduction suggests that impaired GH secretion is a consequence of obesity rather than a pre-existing pituitary-hypothalamic disorder.

An isolated dissecting aneurysm of the superior mesenteric artery : report of a case

We report herein the case of a 56-year-old man found to have an isolated dissecting aneurysm of the superior mesenteric artery (SMA) after he presented with a 3-day history of postprandial epigastralgia of sudden onset. An echogram showed marked dilatation of the SMA and a high level of peripheral echoes in a linear fashion within its lumen. A thin-section contrast enhanced computed tomography revealed a thin flap, separating two distinct well-enhanced lumina. Angiography confirmed the presence of a localized dissecting aneurysm of the SMA. The patient was treated conservatively and has since been followed up as an outpatient. Following the presentation of this case, the problems regarding the diagnosis and management of this rare disease are discussed based on a review of the literature.

Effect of hypothalamic administration of growth hormone-releasing factor (GRF) on feeding behavior in rats.

To examine the role and working site of growth hormone-releasing factor (GRF) in feeding behavior, we first tested the effect of the intracerebroventricular (i.c.v.) injection of GRF on food intake after 24 h of food deprivation. Cumulative food intake was measured 1, 3 and 6 h after injection. A lower dose of GRF stimulated food intake in a dose dependent manner (3 h; GRF 100 pmol 8.64 +/- 1.06 g vs saline 5.50 +/- 0.60 g, P less than 0.05), while a higher dose (1 nmol, 500 pmol) suppressed food intake (3 h; GRF 1 nmol 2.65 +/- 0.70 g vs saline 5.50 +/- 0.60 g, P less than 0.01). Second, the effect of i.c.v. injection of 100 pmol of GRF on peripheral metabolites was examined. The subsequent levels of plasma insulin, glucagon, glucose and non-esterified fatty acid showed no significant difference from those of saline administration. Third, the effect of microinjection of GRF (5 pmol) into several hypothalamic areas on food intake was examined. Injection into the ventromedial hypothalamic nucleus (VMN) stimulated food intake (3 h; GRF 5 pmol 10.32 +/- 1.04 g vs saline 6.92 +/- 0.32 g, P less than 0.05), but no significant effect was observed following injection either into the lateral hypothalamic area (LHA), paraventricular nucleus (PVN) or medial preoptic area (MPOA). Finally, we tested the stimulatory effect of GRF on food intake in bilateral VMN lesioned rats. I.c.v. injection in these animals had no more significant effect on food intake than did saline injection in VMN lesioned rats (3 h; GRF 100 pmol 6.27 +/- 0.87 g vs saline 5.34 +/- 0.44 g).(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatic glucose-sensitive unit regulation of glucose-induced insulin secretion in rats

Vagal glucose receptors, or glucose-sensitive units which modulate insulin secretion, exist in the liver. This study sought to determine the pathway of portal glucose-sensitive unit-regulated insulin secretion by measuring plasma insulin after intraperitoneal (IP) injection of glucose under unanesthetized and unrestrained conditions (Experiment 1), and by recording electrical discharge after intraportal injection of glucose (Experiment 2) in rats with hepatic and/or celiac vagotomy. In Experiment 1, plasma insulin was significantly reduced and plasma glucose elevated after IP glucose injection (1 g/kg) in the three groups of hepatic-, celiac-, and hepatic- and celiac-vagotomized rats in comparison with a sham-vagotomized group. There were no significant differences among the four groups in plasma insulin or glucose after IV glucose injection (0.5 g/kg). In Experiment 2, intraportal injection of 400 mg/dl of glucose solution, a similar concentration to that produced by 1 g/kg of IP glucose injection, caused a reduction in the discharge rate of hepatic vagal afferents and an increase in that of pancreatic vagal efferents. This increase was blocked by prior sectioning of the hepatic branch of the vagus nerve. These results suggested that hepatic glucose-sensitive units enhanced glucose-induced insulin secretion via the hepatic vagal afferents and the pancreatic vagal efferents mediated by the brain stem center in vivo. The physiological role of these hepatic glucose-sensitive units is assumed to maintain blood glucose homeostasis by enhancing glucose-induced insulin secretion.

Amino acid sensors sensitive to alanine and leucine exist in the hepato-portal system in the rat.

We reported the existence of vagal arginine sensors in the liver which modulate arginine-induced pancreatic hormone secretion. The present study was carried out to examine the possible existence of other amino acid sensors such as L-alanine and L-leucine in the hepato-portal system in rats using an electrophysiological approach. Afferent discharges were recorded from fine filaments dissected from the peripheral cut end of the hepatic branch of the vagus nerve. Administration of 0.1, 1, and 10 mM L-alanine and L-leucine solution (0.1 ml) into the portal vein caused an increase in the discharge rate of hepatic vagal afferents in a dose-dependent manner. The results suggest the existence of vagal amino acid sensors which are sensitive to alanine and leucine in the hepato-portal system.

Comparison of DNA contents of visceral organs in rats with ventromedial hypothalamic lesions and fed a high fat diet.

Bilateral lesions of ventromedial hypothalamus are followed by a number of changes including vagal hyperactivity and hyperinsulinemia. To investigate if cell proliferation occurs in visceral organs in rats with ventromedial hypothalamic (VMH) lesions and fed a high fat diet, we determined DNA contents of visceral organs (liver, pancreas, small and large intestines, spleen, kidney and heart) 1 and 4 week after VMH lesions or start of high fat diet. In rats with VMH lesions, DNA contents increased significantly in liver, pancreas, and small and large intestines at 1 week, and maintained the same levels until the 4th week. DNA contents increased most in the pancreas, followed by small and large intestines, and liver. DNA content did not change in spleen, kidney, or heart. In rats fed a high fat diet, there was no increase in the DNA content of these organs, except in the small intestine at 4 weeks. The results suggest that VMH lesions produce excessive DNA synthesis in visceral organs, whereas a high fat diet does not. VMH lesions may induce cell proliferation in visceral organs through vagal hyperactivity and/or changes of humoral growth factors.

Dynamics of blood coagulation factor XIII in ulcerative colitis and preliminary study of the factor XIII concentrate

SummaryBlood coagulation studies were performed in twenty patients with ulcerative colitis (UC). At the active stage of UC, a marked increase in platelet count and fibrinogen concentration, and a marked decrease in Factor XIII activity level were observed. At the active stage of UC, four patients were treated with Factor XIII concentrate leading to reduction of pain, bleeding and endoscopic findings.

Glycine sensors in the hepato-portal system and their reflex effects on pancreatic efferents in the rat

We earlier reported the existence of vagal arginine, alanine, and leucine sensors in the liver which modulate amino acid-induced pancreatic hormone secretion. To determine the possible existence of glycine sensors in the liver and their reflex effects, afferent discharges from the hepatic branch and efferent discharges from the pancreatic branch of the vagus nerve were recorded. Intraportal administration of 0.1, 1, and 10 mM of L-glycine solution (0.1 ml) depressed the afferent discharge rate of the hepatic branch of the nerve in a dose-dependent manner, and increased the efferent discharge rate of the pancreatic vagal branch. The results suggest the existence of glycine sensors in the hepato-portal system that exert reflex regulation on the pancreatic vagus nerve activity.

Role of the efferent and afferent vagus nerve in the development of ventromedial hypothalamic (VMH) obesity

Hyperactivity of the vagus nerve and hypoactivity of the sympathetic nerves after VMH lesions both cooperatively contribute to the development of VMH obesity, mainly through hyperinsulinemia. Recently it has turned out that we should discriminate the role of the efferent vagus from that of the afferent vagus in the pancreatic hormone secretion. The hepatic branch is the main pathway of afferent fibers in the vagus, while the celiac (pancreatic) branch is the main pathway of efferent fibers. We investigated the role of the afferent and efferent vagus on the development of VMH obesity using the sectioning of the hepatic and celiac branch. Celiac vagotomy decreased insulin secretion and food intake, while hepatic vagotomy did not change them. The results suggested that the efferent vagus plays the main role in the development of VMH obesity, while the role of afferent vagus seems less apparent.

Age-related decrease in plasma growth hormone: Response to growth hormone-releasing hormone, arginine, and l-dopa in obesity

Aging is associated with a reduction in plasma growth hormone (GH) secretion in non-obese subjects. To determine whether or not age-related changes in plasma GH secretion exist in obese subjects, we measured (a) plasma GH response to growth hormone-releasing hormone (GRH; 1 microgram/kg body wt), arginine (0.5 g/kg body wt), L-dopa (500 mg), and (b) plasma glucose, insulin, and free fatty acids (FFAs) in 26 fasted obese subjects of various ages ranging from 16 to 71 years. Only subjects with a body mass index (BMI; kg/m2) between 30.0 and 39.0 were studied. Six subjects were adolescents, 9 were in their 20s, and 11 were 30 years or older. The mean peak levels of plasma GH in response to GRH, arginine, and L-dopa in obese subjects were 11.3 +/- 2.1, 21.9 +/- 4.4, and 5.2 +/- 0.3 ng/mL in adolescents, 8.2 +/- 1.6, 9.1 +/- 1.5, and 3.1 +/- 0.6 ng/mL in those in their 20s, and 4.5 +/- 0.4, 7.3 +/- 1.4, and 2.8 +/- 0.3 ng/mL in those 30 years or older, respectively, showing a significant decrease in peak GH level with advancing age (P less than .05 to P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)