Angiotensin receptor blockers improve insulin resistance in type 2 diabetic rats by modulating adipose tissue.
Adipose tissue is recognized as a pivotal organ in the development of insulin resistance. This study seeks to determine the effect of angiotensin receptor blockade (ARB) on insulin resistance of adipocytes in culture and in a rat model of type 2 diabetes. Treatment of Otsuka Long-Evans Tokushima Fatty rats with the ARB L158809 for six months significantly lowered fasting plasma glucose, cholesterol and triglyceride levels but led to higher plasma adiponectin levels. Insulin resistance, measured by an intraperitoneal glucose tolerance test, of the treated rats was significantly improved along with an increase in the number of small differentiated adipocytes; however, epididymal fat mass decreased. Treatment significantly lowered lipid peroxidation and MCP-1 expression while increasing adiponectin production by the adipose tissue. ARB treatment significantly improved insulin sensitivity and markedly suppressed AT2-induced oxidative stress, PAI-1 and MCP-1 levels and NF-kappaB activation of adipocytes in culture. Treatment increased adiponectin and PPARgamma expression along with intracellular triglyceride levels reflecting differentiation of the cultured adipocytes. Our study suggests that ARB treatment improves insulin resistance by modification of adipose tissue thereby blunting the development of diabetes.
Lee
Mi H
MH
Department of Internal Medicine, Korea University, Ansan City, Kyungki-Do, Republic of Korea.
Song
Hye K
HK
Ko
Gang J
GJ
Kang
Young S
YS
Han
Sang Y
SY
Han
Kum H
KH
Kim
Hyoung K
HK
Han
Jee Y
JY
Cha
Dae R
DR
D000273:Adipose Tissue / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D007333:Insulin Resistance; D023421:Models, Animal; D051381:Rats; D020334:Rats, Inbred OLETF
D057911:Angiotensin Receptor Antagonists; D001786:Blood Glucose