Impaired Processing of Prohormones Associated with Abnormalities of Glucose Homeostasis and Adrenal Function

Insulin, the central hormone controlling the utilization of fuel, is initially synthesized in pancreatic beta cells as its relatively inactive precursor, proinsulin. A series of enzymes that process prohormones act on proinsulin to produce mature insulin and C peptide. Abnormalities in the secretory products of beta cells are a rare but well-documented cause of impairment in glucose tolerance and hyperinsulinemia.1 Two specific syndromes have been defined. First, mutations in the insulin gene that lead to the production of biologically ineffective insulin have been described in several families.2–4 All cases described to date have involved heterozygotes who produce normal insulin . . .