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Fat-induced liver insulin resistance
Pankaj Shah1, Ananda Basu, Robert Rizza
1Mayo Clinic and Foundation, 200 First Street SW, Room 5-194 Joseph, Rochester, MN 55905, USA.
Current Diabetes Reports
|May 24, 2003
Summary
Free fatty acids (FFAs) significantly impact liver glucose metabolism by influencing glucose production and uptake. Understanding FFA regulation is crucial for managing metabolic disorders like diabetes.
Area of Science:
- Metabolic regulation
- Hepatic glucose homeostasis
- Endocrinology
Background:
- Free fatty acids (FFAs) are recognized regulators of hepatic glucose metabolism.
- Elevated FFAs can increase hepatic glucose release and decrease glucose uptake.
- Plasma FFAs correlate with endogenous glucose production (EGP) in vivo.
Purpose of the Study:
- To elucidate the role of FFAs in hepatic glucose metabolism.
- To investigate the impact of FFAs on glucose production and uptake.
- To understand FFA effects on EGP, especially in impaired insulin secretion conditions.
Main Methods:
- In vitro studies on enzyme activity (glucose-6-phosphatase, glucokinase).
- In vivo studies in animals and humans correlating plasma FFAs and EGP.
- Intervention studies examining gluconeogenesis and glycogenolysis contributions to EGP.
Main Results:
- FFAs increase hepatic glucose release via glucose-6-phosphatase and gluconeogenic enzymes.
- FFAs may decrease hepatic glucose uptake by reducing glucokinase activity.
- FFA effects on EGP are pronounced when insulin secretion is impaired or prevented.
Conclusions:
- FFAs play a critical role in regulating hepatic glucose production and uptake.
- FFA-induced changes in EGP are significant, particularly in conditions like diabetes mellitus.
- The impact of elevated FFAs on splanchnic glucose uptake differs between healthy individuals and those with type 2 diabetes.