PYY3-36 reinforces insulin action on glucose disposal in mice fed a high-fat diet.
Peptide YY(3-36) (PYY(3-36)) is released by the gut in response to nutrient ingestion. It modulates the activities of orexigenic neuropeptide Y (NPY) neurons and anorexigenic proopiomelanocortin (POMC) neurons in the hypothalamus to inhibit food intake. Because both NPY and POMC have also been shown to impact insulin action, we wondered whether PYY(3-36) could improve insulin sensitivity. To address this question, we examined the acute effect of intravenous PYY(3-36) on glucose and free fatty acid (FFA) flux during a hyperinsulinemic-euglycemic clamp in mice maintained on a high-fat diet for 2 weeks before the experiment. We also evaluated the effects of PYY(3-36) infusion on glucose uptake in muscle and adipose tissue in this experimental context. Under basal conditions, none of the metabolic parameters were affected by PYY(3-36). Under hyperinsulinemic conditions, glucose disposal was significantly increased in PYY(3-36)-infused compared with vehicle-infused mice (103.8 +/- 10.9 vs. 76.1 +/- 11.4 micromol.min(-1).kg(-1), respectively; P = 0.001). Accordingly, glucose uptake in muscle and adipose tissue was greater in PYY(3-36)-treated animals, although the difference with controls did not reach statistical significance in adipose tissue (muscle: 2.1 +/- 0.5 vs. 1.5 +/- 0.5 micromol/g tissue, P = 0.049; adipose tissue: 0.8 +/- 0.4 vs. 0.4 +/- 0.3 micromol/g tissue, P = 0.08). In contrast, PYY(3-36) did not impact insulin action on endogenous glucose production or FFA metabolism. These data indicate that PYY(3-36) reinforces insulin action on glucose disposal in mice fed a high-fat diet, through a mechanism that is independent of food intake and body weight. In contrast, it leaves glucose production and lipid flux largely unaffected in this experimental context.
van den Hoek
Anita M
AM
TNO Prevention and Health, Gaubius Laboratory, Leiden, Netherlands.
Heijboer
Annemieke C
AC
Corssmit
Eleonora P M
EP
Voshol
Peter J
PJ
Romijn
Johannes A
JA
Havekes
Louis M
LM
Pijl
Hanno
H
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D004041:Dietary Fats; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006946:Hyperinsulinism; D007275:Injections, Intravenous; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments; D019894:Peptide YY / Q000008:administration & dosage / Q000494:pharmacology*
D001786:Blood Glucose; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D010446:Peptide Fragments; D019894:Peptide YY; C061785:peptide YY (3-36); D005947:Glucose