Silencing of GPR183 in INS-1 cells decreased the expression of proinsulin genes, Pdx1, Mafa and impaired insulin secretion with a concomitant decrease in cAMP generation.
Increased hepatic lipid content and impaired proinsulin conversion are new predictors, independent of change in body weight, for non-response to lifestyle intervention in addition to the confirmed factors, impaired insulin secretion and insulin sensitivity.
Impaired glucose tolerance and impaired insulin secretion have been reported in families with PAX6 mutations and it is suggested that they result from defective proinsulin processing due to lack of prohormone convertase 1/3, encoded by PCSK1.
However, both aspects of beta cell function are not necessarily linked, as impaired insulin secretion is specifically present in variants of HHEX and impaired proinsulin conversion is specifically present in a variant of SLC30A8.
After glucose infusion, diabetic and non-diabetic subjects had similar intact proinsulin concentrations (geometric mean 4.9 and 5.2 pmol/l, respectively), but the diabetic group had impaired insulin secretion by immunoradiometric assay (geometric means 55 and 101 pmol/l, p less than 0.05) or by radioimmunoassay C-peptide (geometric means 935 and 1410 pmol/l, p less than 0.05), though not by radioimmunoassay insulin (87 and 144 pmol/l, p = 0.12), respectively.