PYY3-36 reinforces insulin action on glucose disposal in mice fed a high-fat diet
article
Peptide YY3-36 (PYY3-36) 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 PYY3-36 could improve insulin sensitivity. To address this question, we examined the acute effect of intravenous PYY3-36 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 PYY3-36 infusion on glucose uptake in muscle and adipose tissue in this experimental context. Under basal conditions, none of the metabolic parameters were affected by PYY3-36. 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 μmol · min-1 · kg -1, respectively; P = 0.001). Accordingly, glucose uptake in muscle and adipose tissue was greater in PYY3-36-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 μmol/g tissue, P = 0.049; adipose tissue: 0.8 ± 0.4 vs. 0.4 ± 0.3 μmol/g tissue, P = 0.08). In contrast, PYY3-36 did not impact insulin action on endogenous glucose production or FFA metabolism. These data indicate that PYY3-36 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. Chemicals / CAS: neuropeptide Y, 82785-45-3, 83589-17-7; peptide YY, 81858-94-8; proopiomelanocortin, 66796-54-1; glucose, 50-99-7, 84778-64-3; insulin, 9004-10-8; Blood Glucose; Dietary Fats; Fatty Acids, Nonesterified; Glucose, 50-99-7; Insulin, 11061-68-0; peptide YY (3-36), 123583-37-9; Peptide YY, 106388-42-5
Topics
Biomedical Researchneuropeptide Ypeptide YYpeptide YY[3-36]proopiomelanocortinunclassified drugfatty acidglucoseinsulinpeptide YY (3 36)peptide YY (3-36)adipose tissueanimal cellanimal experimentanimal modelanimal tissuebody weightcontrolled studyfatty acid transportfood intakeglucose transporthypothalamusinsulin sensitivitylipid dietmousemuscle tissuenonhumananimalbloodC57BL mousediet restrictiondrug effectfat intakeglucose blood levelglucose clamp techniquehyperinsulinismintravenous drug administrationmetabolismskeletal muscletransport at the cellular levelAdipose TissueAnimalsBiological TransportBlood GlucoseDietary FatsFastingFatty Acids, NonesterifiedGlucoseGlucose Clamp TechniqueHyperinsulinismInjections, IntravenousInsulinMaleMiceMice, Inbred C57BLMuscle, SkeletalPeptide YY
TNO Identifier
237934
ISSN
00121797
Source
Diabetes, 53(8), pp. 1949-1952.
Pages
1949-1952
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