Machi Furuta

The angiotensin II receptor blocker telmisartan improves insulin resistance and has beneficial effects in hypertensive patients with type 2 diabetes and poor glycemic control.

The angiotensin II receptor blocker (ARB) telmisartan has a molecular structure that confers it partial agonist properties similar to those of peroxisome proliferators-activated receptor-gamma molecule, which is thought to modulate tissue response to insulin. In order to investigate the effects of telmisartan on insulin sensitivity and glucose metabolism, we enrolled 14 hypertensive patients under treatment with ARB other than telmisartan who had insulin resistance [homeostasis model for insulin resistance (HOMA-IR)>2.0] but no severe glucose tolerance (HbA1c<6.5%), and HOMA-IR was compared before and after the displacement by telmisartan. We also enrolled 27 obese (body mass index>25kg/m(2)) and hypertensive patients with type 2 diabetes under treatment with ARB other than telmisartan, and HbA1c was assessed before and after the displacement by telmisartan. The telmisartan significantly improved HOMA-IR in hypertensive patients and also significantly decreased HbA1c in type 2 diabetic patients especially in the patients with poor glycemic control (HbA1c>==8.0%). These results indicate that telmisartan improves insulin resistance and gives beneficial effects in hypertensive patients with type 2 diabetes and a poor glycemic control.

Effect of exposure to non-esterified fatty acid on progressive deterioration of insulin secretion in patients with Type 2 diabetes: a long-term follow-up study.

Diabet. Med. 29, 980–985 (2012)

Progressive deterioration of insulin secretion in Japanese type 2 diabetic patients in comparison with those who carry the S20G mutation of the islet amyloid polypeptide gene: A long-term follow-up study.

Aims/Introduction:  In order to clarify the enhanced β‐cell dysfunction in type 2 diabetic patients carrying the S20G mutation of the islet amyloid polypeptide gene (S20G‐patients), we first estimated the decline of insulin secretion in Japanese type 2 diabetic patients without the S20G mutation (non‐S20G‐T2D‐patients) by long‐term observation, and then compared it with that of the S20G‐patients.

Protective Roles of Interferon‐γ in Cardiac Hypertrophy Induced by Sustained Pressure Overload

Background A clear understanding of the molecular mechanisms underlying hemodynamic stress‐initiated cardiac hypertrophy is important for preventing heart failure. Interferon‐γ (IFN‐γ) has been suggested to play crucial roles in various diseases other than immunological disorders by modulating the expression of myriad genes. However, the involvement of IFN‐γ in the pathogenesis of cardiac hypertrophy still remains unclear. Methods and Results In order to elucidate the roles of IFN‐γ in pressure overload–induced cardiac pathology, we subjected Balb/c wild‐type (WT) or IFN‐γ‐deficient (Ifng −/−) mice to transverse aortic constriction (TAC). Three weeks after TAC, Ifng −/− mice developed more severe cardiac hypertrophy, fibrosis, and dysfunction than WT mice. Bone marrow–derived immune cells including macrophages were a source of IFN‐γ in hearts after TAC. The activation of PI3K/Akt signaling, a key signaling pathway in compensatory hypertrophy, was detected 3 days after TAC in the left ventricles of WT mice and was markedly attenuated in Ifng −/− mice. The administration of a neutralizing anti‐IFN‐γ antibody abrogated PI3K/Akt signal activation in WT mice during compensatory hypertrophy, while that of IFN‐γ activated PI3K/Akt signaling in Ifng −/− mice. TAC also induced the phosphorylation of Stat5, but not Stat1 in the left ventricles of WT mice 3 days after TAC. Furthermore, IFN‐γ induced Stat5 and Akt phosphorylation in rat cardiomyocytes cultured under stretch conditions. A Stat5 inhibitor significantly suppressed PI3K/Akt signaling activation in the left ventricles of WT mice, and aggravated pressure overload–induced cardiac hypertrophy. Conclusions The IFN‐γ/Stat5 axis may be protective against persistent pressure overload–induced cardiac hypertrophy by activating the PI3K/Akt pathway.

Protective role of human insulin against the cytotoxicity associated with human mutant S20G islet amyloid polypeptide

Islet amyloid polypeptide (IAPP) is a main component of islet amyloid in type 2 diabetes and cosecreted from β‐cell with insulin. Clinical evidence from the patients with S20G mutation of the IAPP gene, as well as experimental evidence that insulin could inhibit amyloid formation of IAPP, suggests that a gradual reduction of insulin could be related to the cytotoxicity associated with S20G‐IAPP through long‐term deterioration of β‐cells in type 2 diabetes. Our objective was to show an effect of human insulin on S20G‐IAPP associated cytotoxicity.

Combined examination of glyceryl trinitrate-mediated vascular dilation with flow-mediated vascular dilation is essential for assessment of vascular function in type 2 diabetes

In order to characterize the impaired vascular function in type 2 diabetes (DM) patients, we evaluated the flow‐mediated vascular dilation (FMD) with glyceryl trinitrate‐mediated vascular dilation (NMD) using ultrasonography.