Dual Effect of Rosuvastatin on Glucose Homeostasis Through Improved Insulin Sensitivity and Reduced Insulin Secretion

• Statins are beneficial in the treatment of cardiovascular disease (CVD), but these lipid-lowering drugs are associated with increased incidence of new on-set diabetes. The cellular mechanisms behind the development of diabetes by statins are elusive. Here we have treated mice on normal diet (ND) and high fat diet (HFD) with rosuvastatin. Under ND rosuvastatin lowered blood glucose through improved insulin sensitivity and increased glucose uptake in adipose tissue. In vitro rosuvastatin reduced insulin secretion and insulin content in islets. In the beta cell Ca(2+) signaling was impaired and the density of granules at the plasma membrane was increased by rosuvastatin treatment. HFD mice developed insulin resistance and increased insulin secretion prior to administration of rosuvastatin. Treatment with rosuvastatin decreased the compensatory insulin secretion and increased glucose uptake. In conclusion, our data shows dual effects on glucose homeostasis by rosuvastatin where insulin sensitivity is improved, but beta cell function is impaired.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

Nyckelord

Adipose tissue

Beta cell

Ca(2+) measurements

Glucose homeostasis

Glucose uptake

Insulin secretion

Islet

Muscle

OGTT

Statin

Transmission electron microscopy

Adipocytes

Adipose Tissue

Animals

Calcium

Calcium Signaling

Diet

High-Fat

Female

Glucose

Homeostasis

Hydroxymethylglutaryl-CoA Reductase Inhibitors

Insulin

Insulin Resistance

Insulin Secretion

Insulin-Secreting Cells

Mice

Rosuvastatin Calcium

Adipose tissue

Beta cell

Ca measurements

Glucose homeostasis

Glucose uptake

Insulin secretion

Islet

Muscle

OGTT

Statin

Transmission electron microscopy

Ca(2+) measurements

Ogtt

Publikations- och innehållstyp

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