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 Research
neuropeptide Y
peptide YY
peptide YY[3-36]
proopiomelanocortin
unclassified drug
fatty acid
glucose
insulin
peptide YY (3 36)
peptide YY (3-36)
adipose tissue
animal cell
animal experiment
animal model
animal tissue
body weight
controlled study
fatty acid transport
food intake
glucose transport
hypothalamus
insulin sensitivity
lipid diet
mouse
muscle tissue
nonhuman
animal
blood
C57BL mouse
diet restriction
drug effect
fat intake
glucose blood level
glucose clamp technique
hyperinsulinism
intravenous drug administration
metabolism
skeletal muscle
transport at the cellular level
Adipose Tissue
Animals
Biological Transport
Blood Glucose
Dietary Fats
Fasting
Fatty Acids, Nonesterified
Glucose
Glucose Clamp Technique
Hyperinsulinism
Injections, Intravenous
Insulin
Male
Mice
Mice, Inbred C57BL
Muscle, Skeletal
Peptide YY
TNO Identifier
237934
DOI
https://dx.doi.org/10.2337/diabetes.53.8.1949
ISSN
00121797
Source
Diabetes, 53(8), pp. 1949-1952.
Pages
1949-1952
Files
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