Osamu Mokuda

Effect of β-hydroxybutyrate and acetoacetate on insulin and glucagon secretion from perfused rat pancreas

Abstract To elucidate the physiological significance of ketone bodies on insulin and glucagon secretion, the direct effects of β-hydroxybutyrate (BOHB) and acetoacetate (AcAc) infusion on insulin and glucagon release from perfused rat pancreas were investigated. The BOHB or AcAc was administered at concentrations of 10, 1, or 0.1 m m for 30 min at 4.0 ml/min. High-concentration infusions of BOHB and AcAc (10 m m ) produced significant increases in insulin release in the presence of 4.4 m m glucose, but low-concentration infusions of BOHB and AcAc (1 and 0.1 mM) caused no significant changes in insulin secretion from perfused rat pancreas. BOHB (10, 1, and 0.1 m m ) and AcAc (10 and 1 m m ) infusion significantly inhibited glucagon secretion from perfused rat pancreas. These results suggest that physiological concentrations of ketone bodies have no direct effect on insulin release but have a direct inhibitory effect on glucagon secretion from perfused rat pancreas.

Effect of thyroid hormone on somatomedin-C release from perfused rat liver

The effect of thyroid hormone on plasma somatomedin-C (SmC) level and on SmC release from perfused rat liver was investigated. Plasma SmC levels and liver tissue SmC were significantly increased in thyroxine-treated rats. Physiological doses of triiodothyronine increased SmC release and SmC concentration in the perfused rat liver. These results indicate that thyroid hormone directly enhances the synthesis and release of SmC in the rat.

Effect of Diabetes on Triiodothyronine and Reverse Triiodothyronine Production in the Perfused Rat Liver and Kidney

This study was undertaken to elucidate the effect of diabetes on the conversion of T4 to T3 and rT3 in the isolated, perfused rat liver and kidney. The livers and kidneys from streptozocin (STZ)-induced (50 mg/kg i.p. 2 wk before killing) diabetic rats with or without T4 (30 μg/kg s.c. daily) treatment were perfused for 30 min with a synthetic medium containing T4 (6 μg/dl), and production of T3 and rT3 in the tissues was measured by radioimmunoassay. The production of T3 (111 ± 38 ng/g/30 min, mean ± SD) and conversion rate of T4 to T3 (19.7 ± 5.8%) in the liver of diabetic rats without T4 treatment and those (124 ± 41 ng/g/30 min and 21.6 ± 4.9%) in the liver of diabetic rats with T4 treatment were significantly lower than those of controls (196 ± 48 ng/g/30 min and 30.6 ± 5.2%), respectively. The production of rT3 and conversion rate of T4 to rT3 in the liver of diabetic rats with or without T4 treatment were similar to those of controls. The production of T3 and rT3, and conversion rate of T4 to T3 and T4 to rT3, in the kidney of diabetic rats with or without T4 treatment were not significantly different from those of controls. These results suggest that the liver is far more important than the kidney in the overall reduction in the T4 to T3 conversion that occurs in diabetic rats.

Effects of intraduodenal nutrient infusion on insulin response to subsequent intravenous glucose in rats.

To elucidate the so-called incretin effect, the effects of intraduodenal bolus injection of glucose, 0.9% NaCl (saline), amino acids, and triglyceride on insulin response to subsequent intravenous injection of glucose (0.5 g/kg in 10% solution) was investigated in rats. Portal and femoral venous insulin and glucose concentration were simultaneously measured. Significantly higher portal insulin and lower femoral glucose values were observed in intraduodenal glucose or saline injection rats compared with controls (nothing was infused into the duodenum). Peripheral removal of insulin in these rats was not decreased. In the rats with intraduodenal injection of amino acids or triglyceride, slightly higher portal insulin and lower femoral glucose values were observed, but they were not significantly different from controls. These results indicate that incretin effect is provoked by intraduodenal infusion of glucose and saline, and may have some important physiologic role on glucose metabolism in rats in vivo.

Somatomedin-C in the kidney of streptozotocin diabetic rats.

To evaluate the possible role of somatomedin-C, insulin-like growth factor I, in renal hypertrophy in early diabetes, kidney tissue SmC concentrations were measured in streptozotocin-induced (80 mg/kg ip) diabetic rats. Body weight, liver weight, plasma SmC concentration, and SmC concentration in the liver of diabetic rats were significantly lower than those of controls. Seven days after induction of diabetes, the kidney weight (898 +/- 95 mg) in diabetic rats was significantly greater than that in controls (755 +/- 69 mg), while SmC concentration in the kidney of diabetic rats (1.7 +/- 0.3 U/g kidney) was significantly lower than that of control rats (5.4 +/- 0.6 U/g kidney). These results suggest that renal SmC may not have an important role in renal hypertrophy in early stages of diabetes and that renal production of SmC may be impaired by insulin deficiency in rats.

Suppressive effect of intragastric nutrients infusion on insulin release from perfused rat pancreas

Using the isolated and perfused rat pancreas preparations, we examined whether or not the direct transmission of signals from the gastro-duodenum to the pancreatic islets is existent. Pancreases were isolated en bloc with stomach and the proximal portion of duodenum and were perfused without recirculation. After perfusion with 5.5mM glucose in the perfusate for 40 minutes, 1 ml solution of the following nutrients (0.9% and 9% NaCl, 5% and 50% glucose, 5% and 50% fructose) was respectively infused into the stomach. And ten minutes after the infusion, the pancreas was perfused with 16.7 mM glucose for 20 minutes. Although the glucose-induced insulin release was similar to controls in the pancreas with intragastric infusion of 0.9% NaCl, 5% glucose, and 5% fructose, it was significantly lowered in the pancreas with intragastric infusion of 9% NaCl, 50% glucose, and 50% fructose. These results indicate that there is a direct transmission of some signals from the gastro-duodenum to the pancreatic islets through intragastric high osmolarity.

Decreased glucose production from maltose in perfused kidney of streptozotocin diabetic rats.

Abstract To elucidate the role of renal maltase in the metabolism of circulating maltose, glucose production from maltose was investigated in perfused kidney of normal and streptozotocin (STZ) diabetic rats. The kidney was perfused with 150 mg/dl maltose for 30 min and perfusate maltose and glucose were measured. Perfusate glucose concentration in the kidney of control rats gradually increased during perfusion. That in the kidney of diabetic rats was significantly lower than that in controls. Perfusate maltose concentration in the kidney of diabetic rats was significantly higher than that in controls. These results suggest that circulating maltose may enter kidney cells and subsequently metabolized to glucose, and that maltose uptake and glucose production were decreased in the kidney of STZ diabetic rats.