The brain modulates insulin sensitivity in multiple tissues.
Study Goal
The researchers aimed to investigate the effects of a high-fat diet on insulin sensitivity, focusing on its direct and indirect impacts via the central nervous system.
Results Summary
The study found that a high-fat diet induces central insulin resistance, which significantly contributes to overall insulin resistance in liver and peripheral tissues. Therapeutic interventions like topiramate and glucagon-like peptide-1 were shown to mitigate these effects in insulin-resistant mice.
Population
Insulin-resistant mice
Effective Dosage
Not specified
Duration
Not specified
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
circulating insulin | decrease | endogenous glucose production | - | - | inhibits | #1 |
circulating insulin | increase | glucose uptake | - | - | stimulates | #2 |
circulating insulin | increase | fatty acid uptake in adipose tissue | - | - | stimulates | #3 |
High-fat diet | increase | insulin resistance in the central nervous system | - | - | induces | #4 |
topiramate | decrease | hepatic and peripheral insulin resistance | insulin resistant mice | - | has central effects on | #5 |
glucagon-like peptide-1 | decrease | hepatic and peripheral insulin resistance | insulin resistant mice | - | has central effects on | #6 |
Insulin sensitivity is determined by direct effects of circulating insulin on metabolically active tissues in combination with indirect effects of circulating insulin, i.e. via the central nervous system. The dose-response effects of insulin differ between the various physiological effects of insulin. At lower insulin concentrations, circulating insulin inhibits endogenous glucose production through a combination of direct and indirect effects. At higher insulin concentrations, circulating insulin also stimulates glucose uptake and fatty acid uptake in adipose tissue, again through direct and indirect effects. High-fat diet induces insulin resistance in the central nervous system, which contributes considerably to overall insulin resistance of liver and peripheral tissues. Central insulin resistance is amendable to therapeutic intervention, reflected in the central effects of topiramate and glucagon-like peptide-1 on hepatic and peripheral insulin resistance in insulin resistant mice.