Enhanced energy expenditure, glucose utilization, and insulin sensitivity in VAMP8 null mice

Haihong Zong, Cheng Chun Wang, Bhavapriya Vaitheesvaran, Irwin J. Kurland, Wanjin Hong, Jeffrey E. Pessin

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

OBJECTIVE: Previous studies have demonstrated that the VAMP8 protein plays a complex role in the control of granule secretion, transport vesicle trafficking, phagocytosis, and endocytosis. The present study was aimed to investigate the role of VAMP8 in mediating GLUT4 trafficking and therefore insulin action in mice. RESEARCH DESIGN AND METHODS: Physiological parameters were measured using Oxymax indirect calorimetry system in 12-week-old VAMP8 null mice. Dynamic analysis of glucose homeostasis was assessed using euglycemic-hyperinsulinemic clamp coupled with tracer radioactively labeled 2-deoxyglucose. Insulin stimulated GLUT4 protein expressions on muscle cell surface were examined by immunofluorescence microscopy. RESULTS: VAMP8 null mice display reduced adiposity with increased energy expenditure despite normal food intake and reduced spontaneous locomotor activity. In parallel, the VAMP8 null mice also had fasting hypoglycemia (84 ± 11 vs. 115 ± 4) and enhanced glucose tolerance with increased insulin sensitivity due to increases in both basal and insulin-stimulated glucose uptake in skeletal muscle (0.19 ± 0.04 vs. 0.09 ± 0.01 mmol/kg/ min during basal, 0.6 ± 0.04 vs. 0.31 ± 0.06 mmol/kg/min during clamp in red-gastrocnemius muscle, P < 0.05). Consistent with a role for VAMP8 in the endocytosis of the insulin-responsive GLUT4, sarcolemma GLUT4 protein levels were increased in both the basal and insulin-stimulated states without any significant change in the total amount of GLUT4 protein or related facilitative glucose transporters present in skeletal muscle, GLUT1, GLUT3, and GLUT11. CONCLUSIONS: These data demonstrate that, in the absence of VAMP8, the relative subcellular distribution of GLUT4 is altered, resulting in increased sarcolemma levels that can account for increased glucose clearance and insulin sensitivity.

Original languageEnglish (US)
Pages (from-to)30-38
Number of pages9
JournalDiabetes
Volume60
Issue number1
DOIs
StatePublished - Jan 2011

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Energy Metabolism
Glucose Transporter Type 4
Insulin Resistance
Insulin
Glucose
Sarcolemma
Skeletal Muscle
Endocytosis
Transport Vesicles
Indirect Calorimetry
Glucose Clamp Technique
Facilitative Glucose Transport Proteins
Deoxyglucose
Adiposity
Locomotion
Fluorescence Microscopy
Phagocytosis
Hypoglycemia
Muscle Cells
Homeostasis

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Enhanced energy expenditure, glucose utilization, and insulin sensitivity in VAMP8 null mice. / Zong, Haihong; Wang, Cheng Chun; Vaitheesvaran, Bhavapriya; Kurland, Irwin J.; Hong, Wanjin; Pessin, Jeffrey E.

In: Diabetes, Vol. 60, No. 1, 01.2011, p. 30-38.

Research output: Contribution to journalArticle

Zong, Haihong ; Wang, Cheng Chun ; Vaitheesvaran, Bhavapriya ; Kurland, Irwin J. ; Hong, Wanjin ; Pessin, Jeffrey E. / Enhanced energy expenditure, glucose utilization, and insulin sensitivity in VAMP8 null mice. In: Diabetes. 2011 ; Vol. 60, No. 1. pp. 30-38.
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abstract = "OBJECTIVE: Previous studies have demonstrated that the VAMP8 protein plays a complex role in the control of granule secretion, transport vesicle trafficking, phagocytosis, and endocytosis. The present study was aimed to investigate the role of VAMP8 in mediating GLUT4 trafficking and therefore insulin action in mice. RESEARCH DESIGN AND METHODS: Physiological parameters were measured using Oxymax indirect calorimetry system in 12-week-old VAMP8 null mice. Dynamic analysis of glucose homeostasis was assessed using euglycemic-hyperinsulinemic clamp coupled with tracer radioactively labeled 2-deoxyglucose. Insulin stimulated GLUT4 protein expressions on muscle cell surface were examined by immunofluorescence microscopy. RESULTS: VAMP8 null mice display reduced adiposity with increased energy expenditure despite normal food intake and reduced spontaneous locomotor activity. In parallel, the VAMP8 null mice also had fasting hypoglycemia (84 ± 11 vs. 115 ± 4) and enhanced glucose tolerance with increased insulin sensitivity due to increases in both basal and insulin-stimulated glucose uptake in skeletal muscle (0.19 ± 0.04 vs. 0.09 ± 0.01 mmol/kg/ min during basal, 0.6 ± 0.04 vs. 0.31 ± 0.06 mmol/kg/min during clamp in red-gastrocnemius muscle, P < 0.05). Consistent with a role for VAMP8 in the endocytosis of the insulin-responsive GLUT4, sarcolemma GLUT4 protein levels were increased in both the basal and insulin-stimulated states without any significant change in the total amount of GLUT4 protein or related facilitative glucose transporters present in skeletal muscle, GLUT1, GLUT3, and GLUT11. CONCLUSIONS: These data demonstrate that, in the absence of VAMP8, the relative subcellular distribution of GLUT4 is altered, resulting in increased sarcolemma levels that can account for increased glucose clearance and insulin sensitivity.",
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AU - Zong, Haihong

AU - Wang, Cheng Chun

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AU - Hong, Wanjin

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