Fig. 6: SIK2 promotes human β cell function.
a Western blots showing levels of SIK2 protein and HSP90 loading control in isolated human islets from non-diabetic human subjects of increasing BMI. b Line plot showing a correlation between SIK2 levels in isolated human islets and subject’s BMI; r2 = 0.52. c Western blots showing levels of CDKN1B protein and ERK2 loading control in isolated human islets from non-diabetic human subjects of increasing BMI. d Line plot showing a correlation between SIK2 levels in isolated human islets and subject’s BMI; r2 = 0.76. e Western blot showing levels of SIK2 and its substrate CDK5R1/p35 following silencing of SIK2 compared to NT control. f Barplots showing insulin secretion in response to 16.7 mM glucose following silencing of SIK2 in isolated human islets compared to NT control. p-value = 0.0327. g Insulin content in islets shown in (f). h Barplot showing the effect of SIK-in on GSIS in isolated human islets compared to DMSO control. p-value = 0.0364. i Insulin content in islets shown in (h). For (f)–(i), bar plots are representative of n = 3 donors. For each plot, error bars are defined as the standard error of the mean of three technical replicates. j Model showing GPR3 promoting CDKN1B accumulation to maintain cell cycle arrest via inhibition of SIK2. When GPR3 is silenced, SIK2 becomes active and CDKN1B is lost, facilitating cell cycle entry. MWs for Western blot markers are in kDa.
