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Opposing effects of reduced kidney mass on liver and skeletal muscle insulin sensitivity in obese mice


Chin, Siew Hung; Item, Flurin; Wueest, Stephan; Zhou, Zhou; Wiedemann, Michael S F; Gai, Zhibo; Schoenle, Eugen J; Kullak-Ublick, Gerd A; Al-Hasani, Hadi; Konrad, Daniel (2015). Opposing effects of reduced kidney mass on liver and skeletal muscle insulin sensitivity in obese mice. Diabetes, 64(4):1131-1141.

Abstract

Reduced kidney mass and/or function may result in multiple metabolic derangements, including insulin resistance. However, underlying mechanisms are poorly understood. Herein, we aimed to determine the impact of reduced kidney mass on glucose metabolism in lean and obese mice. To that end, seven-week-old C57BL6/J mice underwent uninephrectomy (UniNx) or sham operation. After surgery, animals were fed either a chow (standard) or a high fat diet (HFD) and glucose homeostasis was assessed 20 weeks after surgery. Intraperitoneal glucose tolerance was similar in sham-operated and UniNx mice. However, insulin-stimulated glucose disposal in vivo was significantly diminished in UniNx mice, whereas insulin-stimulated glucose uptake into isolated skeletal muscle was similar in sham-operated and UniNx mice. Of note, capillary density was significantly reduced in skeletal muscle of HFD-fed UniNx mice. In contrast, hepatic insulin sensitivity was improved in UniNx mice. Furthermore, adipose tissue HIF1α-expression and inflammation was reduced in HFD-fed UniNx mice. Treatment with the angiotensin II receptor blocker telmisartan improved glucose tolerance and hepatic insulin sensitivity in HFD-fed sham-operated but not UniNx mice. In conclusion, UniNx protects from obesity-induced adipose tissue inflammation and hepatic insulin resistance but it reduces muscle capillary density and, thus, deteriorates HFD-induced skeletal muscle glucose disposal.

Abstract

Reduced kidney mass and/or function may result in multiple metabolic derangements, including insulin resistance. However, underlying mechanisms are poorly understood. Herein, we aimed to determine the impact of reduced kidney mass on glucose metabolism in lean and obese mice. To that end, seven-week-old C57BL6/J mice underwent uninephrectomy (UniNx) or sham operation. After surgery, animals were fed either a chow (standard) or a high fat diet (HFD) and glucose homeostasis was assessed 20 weeks after surgery. Intraperitoneal glucose tolerance was similar in sham-operated and UniNx mice. However, insulin-stimulated glucose disposal in vivo was significantly diminished in UniNx mice, whereas insulin-stimulated glucose uptake into isolated skeletal muscle was similar in sham-operated and UniNx mice. Of note, capillary density was significantly reduced in skeletal muscle of HFD-fed UniNx mice. In contrast, hepatic insulin sensitivity was improved in UniNx mice. Furthermore, adipose tissue HIF1α-expression and inflammation was reduced in HFD-fed UniNx mice. Treatment with the angiotensin II receptor blocker telmisartan improved glucose tolerance and hepatic insulin sensitivity in HFD-fed sham-operated but not UniNx mice. In conclusion, UniNx protects from obesity-induced adipose tissue inflammation and hepatic insulin resistance but it reduces muscle capillary density and, thus, deteriorates HFD-induced skeletal muscle glucose disposal.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Clinical Pharmacology and Toxicology
Dewey Decimal Classification:610 Medicine & health
Date:2015
Deposited On:17 Nov 2014 17:17
Last Modified:08 Dec 2017 08:10
Publisher:American Diabetes Association
ISSN:0012-1797
Additional Information:This is an author-created, uncopyedited electronic version of an article accepted for publication in Diabetes (http://diabetes.diabetesjournals.org). The American Diabetes Association (ADA), publisher of Diabetes, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version is available online at DOI 10.2337/db14-0779
Publisher DOI:https://doi.org/10.2337/db14-0779
PubMed ID:25325737

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