Chronic angiotensin-(1-7) improves insulin sensitivity in high-fat fed mice independent of blood pressure

Ian M. Williams, Yolanda F. Otero, Deanna P. Bracy, David H. Wasserman, Italo Biaggioni, Amy C. Arnold

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Angiotensin-(1-7) improves glycemic control in animal models of cardiometabolic syndrome. The tissue-specific sites of action and blood pressure dependence of these metabolic effects, however, remain unclear. We hypothesized that Ang-(1-7) improves insulin sensitivity by enhancing peripheral glucose delivery. Adult male C57BL/6J mice were placed on standard chow or 60% high-fat diet for 11 weeks. Ang-(1-7) (400 ng/kg per minute) or saline was infused subcutaneously during the last 3 weeks of diet, and hyperinsulinemic-euglycemic clamps were performed at the end of treatment. High-fat fed mice exhibited modest hypertension (systolic blood pressure: 137±3 high fat versus 123±5 mm Hg chow; P=0.001), which was not altered by Ang-(1-7) (141±4 mm Hg; P=0.574). Ang-(1-7) did not alter body weight or fasting glucose and insulin in chow or high-fat fed mice. Ang-(1-7) increased the steady-state glucose infusion rate needed to maintain euglycemia in high-fat fed mice (31±5 Ang-(1-7) versus 16±1 mg/kg per minute vehicle; P=0.017) reflecting increased whole-body insulin sensitivity, with no effect in chow-fed mice. The improved insulin sensitivity in high-fat fed mice was because of an enhanced rate of glucose disappearance (34±5 Ang-(1-7) versus 20±2 mg/kg per minute vehicle; P=0.049). Ang-(1-7) enhanced glucose uptake specifically into skeletal muscle by increasing translocation of glucose transporter 4 to the sarcolemma. Our data suggest that Ang-(1-7) has direct insulin-sensitizing effects on skeletal muscle, independent of changes in blood pressure. These findings provide new insight into mechanisms by which Ang-(1-7) improves insulin action, and provide further support for targeting this peptide in cardiometabolic disease.

Original languageEnglish (US)
Pages (from-to)983-991
Number of pages9
JournalHypertension
Volume67
Issue number5
DOIs
StatePublished - May 1 2016

Fingerprint

Insulin Resistance
Fats
Blood Pressure
Glucose
Insulin
Skeletal Muscle
Sarcolemma
Glucose Clamp Technique
Facilitative Glucose Transport Proteins
High Fat Diet
Inbred C57BL Mouse
Fasting
Animal Models
Body Weight
angiotensin I (1-7)
Diet
Hypertension
Peptides
Therapeutics

All Science Journal Classification (ASJC) codes

  • Internal Medicine

Cite this

Williams, Ian M. ; Otero, Yolanda F. ; Bracy, Deanna P. ; Wasserman, David H. ; Biaggioni, Italo ; Arnold, Amy C. / Chronic angiotensin-(1-7) improves insulin sensitivity in high-fat fed mice independent of blood pressure. In: Hypertension. 2016 ; Vol. 67, No. 5. pp. 983-991.
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abstract = "Angiotensin-(1-7) improves glycemic control in animal models of cardiometabolic syndrome. The tissue-specific sites of action and blood pressure dependence of these metabolic effects, however, remain unclear. We hypothesized that Ang-(1-7) improves insulin sensitivity by enhancing peripheral glucose delivery. Adult male C57BL/6J mice were placed on standard chow or 60{\%} high-fat diet for 11 weeks. Ang-(1-7) (400 ng/kg per minute) or saline was infused subcutaneously during the last 3 weeks of diet, and hyperinsulinemic-euglycemic clamps were performed at the end of treatment. High-fat fed mice exhibited modest hypertension (systolic blood pressure: 137±3 high fat versus 123±5 mm Hg chow; P=0.001), which was not altered by Ang-(1-7) (141±4 mm Hg; P=0.574). Ang-(1-7) did not alter body weight or fasting glucose and insulin in chow or high-fat fed mice. Ang-(1-7) increased the steady-state glucose infusion rate needed to maintain euglycemia in high-fat fed mice (31±5 Ang-(1-7) versus 16±1 mg/kg per minute vehicle; P=0.017) reflecting increased whole-body insulin sensitivity, with no effect in chow-fed mice. The improved insulin sensitivity in high-fat fed mice was because of an enhanced rate of glucose disappearance (34±5 Ang-(1-7) versus 20±2 mg/kg per minute vehicle; P=0.049). Ang-(1-7) enhanced glucose uptake specifically into skeletal muscle by increasing translocation of glucose transporter 4 to the sarcolemma. Our data suggest that Ang-(1-7) has direct insulin-sensitizing effects on skeletal muscle, independent of changes in blood pressure. These findings provide new insight into mechanisms by which Ang-(1-7) improves insulin action, and provide further support for targeting this peptide in cardiometabolic disease.",
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Chronic angiotensin-(1-7) improves insulin sensitivity in high-fat fed mice independent of blood pressure. / Williams, Ian M.; Otero, Yolanda F.; Bracy, Deanna P.; Wasserman, David H.; Biaggioni, Italo; Arnold, Amy C.

In: Hypertension, Vol. 67, No. 5, 01.05.2016, p. 983-991.

Research output: Contribution to journalArticle

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