Obesity: Nishizawa M

Nakano S, Kitazawa M, Ito T, Hatakeyama H, Nishizawa M, Nakagawa A, Kigoshi T, Uchida K. · Division of Endocrinology, Department of Internal Medicine, Kanazawa Medical University, Uchinada, Ishikawa, Japan. · Clin Exp Hypertens. · Pubmed #12716078 No free full text.

Abstract: To elucidate the relationships between obesity, glycemic control, dyslipidemia, hypertension, microvascular complications, and insulin resistance assessed using an euglycemic hyperinsulinemic clamp technique, we studied 54 hospitalized type 2 diabetic subjects (DM) and 10 age- and sex-matched normotensive, nonobese control subjects (C). Glucose infusion rate (GIR) derived from the clamp study was used as an index of insulin resistance. Body mass index (BMI), the prevalence of hypertension, HbA1c and serum nonesterified fatty acids (NEFA) were significantly higher, and serum high-density-lipoprotein (HDL)-cholesterol was significantly lower in DM than in C (p < 0.05 or less). The median GIR level was significantly lower inDM than in C (p = 0.038). The difference in GIR between the two groups wasstill statistically significant even after adjustment for BMI, mean BP, HbA1c, NEFA, and HDL-cholesterol. However, after simultaneous adjustment for these factors, there was no difference in GIR between the two groups. Body mass index, mean BP, HbA1c, and NEFA showed negative correlations, and serum HDL-cholesterol showed a positive correlation with GIR, but neither age nor duration of diabetes correlated with GIR. When GIR values in DM were divided according to the degree of neuropathy, retinopathy, and nephropathy, and compared to those in C, GIR levels tended to be decreased with increasing severity of each microvascular complication, but there was no difference in median GIR levels among the diabetic subgroups. Relationships between the GIR levels and confounding factors such as age, sex, BMI, mean BP, HbA1c, serum NEFA, and serum HDL-cholesterol, were examined simultaneously with a multiple regression analysis. This analysis revealed that HbA1c and serum NEFA may affect the GIR level. Furthermore, together with these two factors, the relationships between the GIR levels and the severity of each microvascular complication were explored with the same analysis. This model clearly demonstrated that both the decreased CVR-R and pronounced orthostatic fall in systolic BP were independent factors for the decreased GIR. These findings suggest that marked autonomic dysfunction, rather than other confounding factors, is related to increased insulin resistance in DM.

Suzuki H, Nishizawa M, Ichikawa M, Kumagai K, Ryuzaki M, Kumagai H, Saruta T, Ikeda H. · Department of Nephrology, Saitama Medical School, Saitama Prefecture, Japan. · J Hypertens. · Pubmed #10419069 No free full text.

Abstract: AIM: Wistar fatty rats (WFR) develop mild hypertension associated with obesity, hyperglycaemia and hyperinsulinaemia, and are thus assumed to be a good model of insulin resistance-related hypertension. We determined whether the activity of the sympathetic nervous system and its baroreflex-mediated regulation are involved in the development of hypertension in this strain. METHODS: Renal sympathetic nerve activity (RSNA) was recorded in pre-hypertensive WFR (n = 8, age 12 weeks) and Wistar lean rats (WLR) (n = 8) during changes in arterial pressure by phenylephrine and nitroprusside infusion in the conscious state. Baroreflex control of RSNA and heart rate were examined by logistic function analysis. RESULTS: The mean arterial pressure (MAP) of WFR was similar to that of WLR (108 +/- 4 versus 101 +/- 2 mmHg, not significant). Basal RSNA was elevated in WFR compared with WLR (86 +/- 2 versus 51 +/- 2% maximum, P< 0.01). Baroreflex control of RSNA was shifted to higher pressure levels (mid-range, 119 +/- 4 versus 99 +/- 4 mmHg, P < 0.05) in WFR compared with WLR, in spite of similar MAP. However, baroreflex sensitivity concerning RSNA was greater in WFR than WLR (3.07 +/- 0.15 versus 1.63 +/- 0.12% maximum/mmHg, P < 0.01). Baroreflex control of heart rate was also shifted to higher pressure levels (mid-range 129 +/- 4 versus 100 +/- 5 mmHg, P < 0.01) and its sensitivity was increased in WFR compared with WLR (4.62 +/- 0.51 versus 3.16 +/- 0.10 bpm/mmHg, P< 0.05). CONCLUSION: These results suggest that baroreflex is not impaired in spite of elevation of blood pressure and that the raised sympathetic nerve activity may contribute to the development of hypertension in WFR.

Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, Matsuki Y, Murakami M, Ichisaka T, Murakami H, Watanabe E, Takagi T, Akiyoshi M, Ohtsubo T, Kihara S, Yamashita S, Makishima M, Funahashi T, Yamanaka S, Hiramatsu R, Matsuzawa Y, Shimomura I. · Department of Medicine and Pathophysiology, Graduate School of Medicine, and Department of Organismal Biosystems, Graduate School of Frontier Biosciences, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. · Science. · Pubmed #15604363 links to  free full text

Abstract: Fat tissue produces a variety of secreted proteins (adipocytokines) with important roles in metabolism. We isolated a newly identified adipocytokine, visfatin, that is highly enriched in the visceral fat of both humans and mice and whose expression level in plasma increases during the development of obesity. Visfatin corresponds to a protein identified previously as pre-B cell colony-enhancing factor (PBEF), a 52-kilodalton cytokine expressed in lymphocytes. Visfatin exerted insulin-mimetic effects in cultured cells and lowered plasma glucose levels in mice. Mice heterozygous for a targeted mutation in the visfatin gene had modestly higher levels of plasma glucose relative to wild-type littermates. Surprisingly, visfatin binds to and activates the insulin receptor. Further study of visfatin's physiological role may lead to new insights into glucose homeostasis and/or new therapies for metabolic disorders such as diabetes.