Insulin resistance (IR) increases with age and plays a key role in the pathogenesis of
type 2 diabetes mellitus. Oxidative stress and
mitochondrial dysfunction are supposed to be major factors leading to age-related IR.
Genipin, an extract from Gardenia jasminoides Ellis fruit, has been reported to stimulate insulin secretion in pancreatic islet cells by regulating mitochondrial function. In this study, we first investigated the effects of
genipin on
insulin sensitivity and the potential mitochondrial mechanisms in the liver of aging rats. The rats were randomly assigned to receive
intraperitoneal injections of either 25mg/kg
genipin or vehicle once daily for 12days. The aging rats showed
hyperinsulinemia and
hyperlipidemia, and
insulin resistance as examined by the decreased
glucose decay constant rate during
insulin tolerance test (kITT). The hepatic tissues showed steatosis and reduced
glycogen content. Hepatic
malondialdehyde level and mitochondrial
reactive oxygen species (ROS) were higher, and levels of mitochondrial membrane potential (
MMP) and
ATP were lower as compared with the normal control rats. Administration of
genipin ameliorated systemic and hepatic
insulin resistance, alleviated
hyperinsulinemia, hyperglyceridemia and hepatic steatosis, relieved hepatic oxidative stress and
mitochondrial dysfunction in aging rats. Furthermore,
genipin not only improved
insulin sensitivity by promoting
insulin-stimulated
glucose consumption and
glycogen synthesis, inhibited cellular ROS overproduction and alleviated the reduction of levels of
MMP and
ATP, but also reversed oxidative stress-associated JNK hyperactivation and reduced Akt phosphorylation in
palmitate-treated L02 hepatocytes. In conclusion,
genipin ameliorates age-related
insulin resistance through inhibiting hepatic oxidative stress and
mitochondrial dysfunction.