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.
TNO Prevention and Health, Gaubius Laboratory, Leiden, Netherlands.
Anita M
AM
van den Hoek
Annemieke C
AC
Heijboer
Eleonora P M
EP
Corssmit
Peter J
PJ
Voshol
Johannes A
JA
Romijn
Louis M
LM
Havekes
Hanno
H
Pijl
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