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Diabetologia. 2013 Mar;56(3):553-62. doi: 10.1007/s00125-012-2801-0. Epub 2012 Dec 19.

Modulation of hypovitaminosis D-induced islet dysfunction and insulin resistance through direct suppression of the pancreatic islet renin-angiotensin system in mice.

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1
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Room 609A, Lo Kwee-Seong Integrated Biomedical Sciences Building, Shatin, Hong Kong Special Administrative Region, People's Republic of China.

Abstract

AIMS/HYPOTHESIS:

Vitamin D is necessary for normal insulin action and suppresses renin production. Increased renin-angiotensin system (RAS) activity causes islet damage, including reduced insulin secretion. We therefore sought to determine whether hypovitaminosis D-induced upregulation of islet RAS in vivo impairs islet cell function and increases insulin resistance, and whether pharmacological suppression of the RAS during continuing vitamin D deficiency might correct this.

METHODS:

C57BL/6 mice were rendered vitamin D-deficient by diet, and glucose and insulin tolerance was assessed. The expression and translation of islet functional, and islet RAS, genes were measured and the effects of pharmacological renin suppression examined.

RESULTS:

Mice with diet-induced hypovitaminosis D developed impaired glucose tolerance, increased RAS component expression and impaired islet function gene transcription. Treatment with pharmacological renin inhibition (aliskiren), without vitamin D status correction, reduced islet RAS over-reactivity, islet dysfunction and insulin resistance, and improved glucose tolerance.

CONCLUSIONS/INTERPRETATION:

Upregulation of islet RAS genes can contribute to hypovitaminosis D-induced impairment of islet function and increase insulin resistance independently of vitamin D status. Thus, our findings support the use of RAS inhibitors in impaired glucose homeostasis or early diabetes. They also suggest that combining RAS inhibition with correction of hypovitaminosis D might be useful in treating impaired glycaemic control and also in type 2 diabetes prevention. However, the use of aliskiren in established diabetes is contraindicated due to the increased risk of side effects such as hyperkalaemia, so other more suitable RAS blockers need to be identified.

PMID:
23250033
DOI:
10.1007/s00125-012-2801-0
[Indexed for MEDLINE]
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