Figure 1. DHT activation of AR in β cell amplifies the insulinotropic effect of islet-derived GLP-1 via GLP-1R.

(A–D) Data are from male βARKO^MIP and AR^lox MIP-CreERT (control) mice fed a western diet since weaning. (A) Random-fed blood glucose and corresponding area under the curve (AUC) from 9 to 29 weeks. (B and C) Random-fed blood glucose and insulin measured at 25 weeks. (D) Insulin/glucose index of insulin deficiency from (B) and (C).

(E) Intraperitoneal glucose-stimulated insulin secretion (GSIS) (3 g/kg) with corresponding insulin AUC.

(F) Intraperitoneal glucose tolerance test (GTT) (2 g/kg) with corresponding glucose AUC.

(G) Intraperitoneal arginine-stimulated insulin secretion (ASIS) (1 g/kg) with corresponding insulin AUC.

(H) Oral GTT (2 g/kg) with corresponding glucose AUC.

(I) Insulin/glucose ratio at 30 min into the oral GTT. Mice were studied at 23–35 weeks of age (n = 10–15).

(J and K) GSIS measured in static incubation in chow-fed RIP-Cre (control), (J) βGLP-1RKO^RIP islets and (K) βARKO^RIP islets treated with DHT (10 nM) and GLP-1 (10 nM) for 40 min. Values represent the mean ± SE of n = 2 mice/group measured in triplicate.

(L) Dynamic insulin secretion measured via perifusion in male human islets challenged with 2.8 mM glucose, 16.7 mM glucose, and 20 mM KCl + 16.7 mM glucose. Islets were cultured overnight in vehicle or DHT (10 nM). During perifusion, islets were treated with vehicle, DHT, Exendin9–39 (100 nM), or DHT + Exendin9–39.

(M) AUC for insulin secretion during 16.7 mM glucose (10–30 min) from (L).

(N) AUC for insulin secretion during second KCl + glucose (45–60 min) from (L).

In (L) to (N), data represent a mean ± SE. of two chambers/donor using n = 3 donors. Values represent the mean ± SE. *p < 0.05, **p < 0.01, ***p < 0.001.