Endocrine Abstracts

Background: Hypovitaminosis D is associated with T2DM risk, cross-sectionally and prospectively; supplementation can reduce insulin resistance and increase glucose-induced insulin secretion in humans. Increased pancreatic islet RAS activity is induced by hyperglycemia, enhancing β cell damage (Leung PS et al.). Vitamin D is now known to suppress renin secretion, thus we have examined effects of calcitriol on increased islet RAS activity in vitro±hyperglycemia and the effects of RAS blockade on islet function during continuing vitamin D deficiency in vivo.

Methods: i) RAS component expression and secretion in islets from WT mice were examined under normal and hyperglycemic conditions and in VDR-KO mice. ii) RAS activity and β cell function were examined in islets from mice with dietary vitamin D deficiency±treatment with aliskrenin.

Results: i) Adding calcitriol to islets before or during exposure to hyperglycemia prevented increases in RAS activity and related disorders, and restored insulin secretion (effects that were optimal @10⁻⁹ molar). ii) RAS blockade in vivo during vitamin D deficiency restored glucose tolerance, reduced overall and postprandial insulin resistance whilst also reducing islet RAS over-activity and related disorders

Comments: Upregulation of RAS activity contributes to islet dysfunction, probably explaining T2DM risk-reduction in RCTs of RAs blockers. Hypovitaminosis D contributes to T2DM risk through avoidable effects on islet RAS activity. Vitamin D and RAS blockade may be additive or synergistic for T2DM risk reduction.

Preliminary studies suggest vitamin D suppression of hepatic RAS may reduce insulin resistance.

RAS suppression may benefit RAS-increasing diabetic complications, like proliferative retinopathy.

Declaration of funding

This work was supported by the General Research Fund from Research Grants Council of Hong Kong (Ref. No: CUHK 470709 and CUHK 468912) awarded to P S Leung. Aliskiren was from Novartis (MTA #33405).