Biomedical subjects

I Kosegawa

Publications and source records attributed to I Kosegawa.

6 recordsLinked to original sources

PubMed1999

Troglitazone and metformin, but not glibenclamide, decrease blood pressure in Otsuka Long Evans Tokushima Fatty rats.

To determine whether hypoglycemic agents such as sulfonylureas, biguanides and the newly developed insulin sensitizers such as troglitazone, have hypotensive effects in an animal model of non-insulin-dependent diabetes mellitus associated with insulin resistance, male Otsuka Long Evans Tokushima Fatty (OLETF) rats aged 12 weeks were administered following hypoglycemic agents or vehicle by gavage for 26 weeks; glibenclamide (5 mg/kg/day), metformin (100 mg/kg/day) and troglitazone (70 mg/kg/day). The gain in body weight was similar in the different groups. At 36 weeks of age, troglitazone significantly decreased fasting plasma glucose levels when compared to controls. The area under the curve (AUC) for insulin during glucose loading (2 g/kg, i.p.) was 50% lower in the group treated with troglitazone. Serum triglyceride levels in troglitazone-treated rats were also significantly lower than in the glibenclamide-treated group. Plasma membrane GLUT4 protein content was significantly augmented by a factor of 1.48-fold (p<0.02) in the glibenclamide-treated group and tended to be increased 1.32 times by administration of metformin (p=0.06). The systolic blood pressure increased with age in controls and the glibenclamide-treated group. In contrast, treatment with either metformin or troglitazone significantly decreased systolic blood pressure after the age of 29 weeks. Plasma norepinephrine and epinephrine concentrations did not show a significant decrease in the treated group when compared with the control group. These results suggest that metformin and troglitazone, but not glibenclamide, lower blood pressure in an animal model of insulin resistance, providing further evidence of the beneficial effect of insulin sensitizing hypoglycemic agents on blood pressure.

Animals↗

PubMed1998

Effect of the vasodilatory beta-blocker, nipradilol, and Ca-antagonist, barnidipine, on insulin sensitivity in patients with essential hypertension.

OBJECTIVES: To assess the effects of a vasodilatory beta-adrenoceptor blocker, nipradilol, and a long-acting Ca channel blocker, barnidipine, on insulin sensitivity. DESIGN: Insulin sensitivity was determined using a euglycemic hyperinsulinemic clamp technique before and after a 12-week treatment period in eighteen patients with essential hypertension. RESULTS: Both drugs decreased blood pressure without affecting any serum parameters of glucose and lipid metabolism. Nipradilol significantly augmented glucose infusion rate (GIR) from 3.11+/-0.28 to 4.69+/-0.57mg/kg/min (p=0.027). Barnidipine also increased GIR from 3.91+/-0.43 to 5.29+/-0.43 mg/kg/min (p=0.028). Plasma norepinephrine concentrations significantly increased with barnidipine treatment, while nipradilol had no effect on plasma norepinephrine levels. No adverse events were reported during the study. CONCLUSIONS: These results suggest that vasodilatory beta-blockers such as nipradilol and long-acting Ca channel blockers such as barnidipine may be useful in the treatment of insulin resistant hypertensive patients.

Adrenergic beta-Antagonists↗

PubMed1996

Metformin decreases blood pressure and obesity in OLETF rats via improvement of insulin resistance.

To determine whether improvement of insulin resistance decreases blood pressure as well as obesity, metformin (100 mg/kg/d) or vehicle was administered for 20 weeks to 12-week-old male Otsuka Long-Evans Tokushima Fatty (OLETF) rats (n = 10 each), a newly developed animal model of non-insulin-dependent diabetes mellitus (NIDDM) with mild obesity, hyperinsulinemia, and hypertriglyceridemia. Oral administration of metformin ameliorated glucose intolerance and attenuated the insulin response to glucose loading (2 g/kg, i.p.), as evidenced by a decrease in the area under the curve for glucose and insulin at 24 weeks by 19% and 37%, respectively. At 21 weeks, systolic blood pressure was significantly lower in the metformin group than in controls (130 +/- 1.9 vs. 143 +/- 2.7 mmHg, p < 0.01), despite no difference in body weight. Subsequently, blood pressure tended to be slightly but insignificantly lower in the metformin group, and body weight was significantly lower in the metformin group (532 +/- 9.8 vs. 587 +/- 10.3 g at 31 weeks, p < 0.01). Metformin treatment also lowered the level of serum triglycerides (9.4 +/- 0.6 vs. 13.2 +/- 0.5 mmol/l, p < 0.01) and the plasma norepinephrine concentration (4,222 +/- 373 vs. 7,548 +/- 1,058 pg/ml, p < 0.01). These results suggest that metformin-induced improvement of insulin resistance in obese rats with NIDDM may lower blood pressure, as well as decrease sympathetic activity and reduce body weight.

Aging↗

PubMed1996

Bradykinin may not be involved in improvement of insulin resistance by angiotensin converting enzyme inhibitor.

We have previously demonstrated that captopril ameliorates glucose intolerance by partially preventing the reduction in postprandial skeletal muscle blood flow. The present study was designed to clarify the mechanism by which ACE inhibitors affect glucose metabolism in fructose (FRU)-fed Wistar rats with hypertension, glucose intolerance and hyperinsulinemia. Eight-week-old male rats (n = 51) were divided into six groups. Controls were given a normal chow, while fructose-rich (55%) chow was administered to the remainder for eight weeks. The different groups were administered alacepril (ALA, 30 mg/kg/day) with or without a continuous infusion of Hoe 140, a kinin B2 receptor antagonist (150 micrograms/kg/day), Hoe 140 alone or TCV-116 (1 mg/kg/day), an angiotensin II receptor antagonist, alone. After measuring the body weight and systolic blood pressure (BP), steady-state plasma glucose (SSPG) levels were determined. FRU significantly increased BP from 141 mmHg in controls to 156 mmHg. ALA with or without Hoe 140 decreased BP to 124 mmHg or 117 mmHg, respectively, but Hoe 140 alone did not affect BP. TCV-116 also decreased BP to 116 mmHg. The SSPG levels increased from 7.58 mM in controls to 8.98 mM in FRU-fed rats. This was lowered with both ALA and TCV-116. Hoe 140 alone, however, did not affect SSPG levels. Hoe 140 did not show any effects on ALA-induced improvement of SSPG. These results suggest that the improvement in glucose tolerance observed with ACE inhibitors is not due to the kinins, and angiotensin II receptor antagonists also improve insulin sensitivity.

Angiotensin Receptor Antagonists↗

PubMed1994

Evidence against a role of insulin in hypertension in spontaneously hypertensive rats. CS-045 does not lower blood pressure despite improvement of insulin resistance.

Hyperinsulinemia resulting from peripheral insulin resistance has been demonstrated both in spontaneously hypertensive rats (SHR) and in humans with essential hypertension. A new class of antidiabetic drugs, thiazolidinediones, which can improve insulin resistance, may be able to lower not only blood glucose levels but also blood pressure. The present study was therefore designed to clarify the proportion of SHR that are glucose intolerant and to observe the effect on blood pressure of CS-045 (troglitazone) administered at 70 mg/kg per day for 2 weeks to male SHR (n = 13). Among 67 male 8-week-old SHR, 74.6% were glucose intolerant and hyperinsulinemic. Systolic blood pressure did not correlate with plasma glucose or insulin levels before or after glucose loading. Treatment with CS-045 improved insulin resistance, as evidenced by a smaller area under the curve of plasma glucose and insulin levels in response to glucose loading. However, systolic blood pressure was not altered. When the data were reanalyzed according to the presence or absence of glucose intolerance before the treatment, blood pressure in the treated group was the same as in controls despite significant improvement in steady-state plasma glucose levels. These results suggest that hyperinsulinemia and/or insulin resistance may not be involved in the development or maintenance of hypertension in SHR, which is in contrast to models of hypertension such as obese Zucker rats or fructose-fed rats.

Animals↗

PubMed1991

Blood ketone bodies in NIDDM: relationship with diabetic control and endogenous insulin secretion.

To evaluate the relationship of blood ketone bodies with diabetic control and endogenous insulin secretion, fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), fasting serum C-peptide (CPR), blood total ketone-bodies (TKB), blood acetoacetate (AcAc) and blood 3-hydroxybutyrate (3-OHB) were compared in 78 outpatients with non-insulin-dependent diabetes mellitus (NIDDM) treated with diet (n = 13), sulfonylurea (n = 52) and insulin (n = 13). TKB, AcAc and 3-OHB in patients treated with insulin were significantly higher than in patients treated with diet or sulfonylurea. In patients given diet therapy, log 3-OHB showed significant negative correlations with FPG, HbA1c and CPR. In patients treated with sulfonylurea, log 3-OHB showed significant positive correlations with FPG and HbA1c, but not with CPR. In patients treated with insulin, there were no correlations of log 3-OHB with FPG, HbA1c and CPR. For evaluation of the metabolic state in diabetes mellitus, measurement of blood ketone bodies is useful, and moreover necessary, in addition to diabetic control or determination of the endogenous insulin level.

3-Hydroxybutyric Acid↗