J Korean Diabetes Assoc.  1997 Jun;21(2):168-175.

Mechanism of Insulin Resistance : Time Dependence of the Development of Insulin Resistance in High Fat Fed Rats

• Park KS
• Lee KU
• Park SW
• Lee HK
• Min HK

Abstract

BACKGROUND: Increased FFA availability is known to induce insulin resistance by decrease in peripheral glucose utilization and increase in hepatic glucose procluction. However, there are conflicting results about the time dependence of the developrnent of insulin resistance with increased availability of FFA.
METHODS
To elucidate the time dependence of the development of insulin resistance associated with increased availability of FFA, peripheral glucose utilization rate and hepatic glucose production rate were measured by euglycemic hyperinsulinemic clamp with 3-3H glucose infusion in rats fed high fat diet (1 week or 3 weeks) or control diet(ordinary chow diet).
RESULTS
Basal plasrna FFA levels and steady state plasma insulin levels increased after high fat diet. After 1 week of high fat diet, suppressibility of hepatic glucose production rate by insulin was impaired(p<0.05 vs control). Insulin sensitivity index(glucose utilization rates/steady state plasma insulin concentrmtions X100) was decreased only after 3 weeks of high fat diet(p<0.05 vs control) which was accompanied by decreased glycogen synthase activity.
CONCLUSION
High fat diet induces hepatic insulin resistance before peripheral insulin resistance and decreased glycogen synthase activity may contribute to the development of peripheral insulin resistance in rats fed high fat diet.

Keyword

High fat diet; Euglycemic hyperinsulinemic clamp; Peirpheral glucose utilization; Hepatic glucose production; Insulin resistance; Glycogen synthase

MeSH Terms

Animals
Diet, High-Fat
Glucose
Glycogen Synthase
Insulin Resistance*
Insulin*
Plasma
Rats*
Glucose
Glycogen Synthase
Insulin