The effect of sugars on (pro)insulin biosynthesis

Abstract

Rates of incorporation of [4,5-(3)H]leucine into insulin plus proinsulin, designated ;(pro)insulin', and total protein in rat pancreatic islets were measured. Glucose stimulates rates of total protein and (pro)insulin biosynthesis, but (pro)insulin biosynthesis is stimulated preferentially. Mannose and N-acetylglucosamine also stimulate (pro)insulin and total protein biosynthesis; inosine and dihydroxyacetone stimulate (pro)insulin biosynthesis specifically. Fructose does not stimulate (pro)insulin biosynthesis when tested alone, but does so in the presence of low concentrations of glucose, mannose or N-acetylglucosamine. Many glucose analogues do not stimulate (pro)insulin biosynthesis. Mannoheptulose inhibits synthesis of (pro)insulin and total protein stimulated by glucose or mannose but not by dihydroxyacetone, inosine or N-acetylglucosamine; phloretin (9mum) inhibits N-acetylglucosamine-stimulated (pro)insulin biosynthesis preferentially. The data are in agreement with the view that the same glucose-sensor mechanism may control both insulin release and biosynthesis, and ;substrate-site' model is suggested. The threshold for stimulation of biosynthesis of (pro)insulin and total protein is lower than that found for glucose-stimulated insulin release; moreover the biosynthetic response to an elevation of glucose concentration is slower than that found for insulin release. The physiological implication of these findings is discussed. Caffeine and isobutylmethylxanthine, at concentrations known to increase islet 3':5'-cyclic AMP and potentiate glucose-induced insulin release, were without effect on rates of glucose-stimulated (pro)insulin biosynthesis.

Glucose regulates preproinsulin messenger RNA levels in a clonal cell line of simian virus 40‐transformed B cells

“…Thus, like insulin biosynthesis [22], glucose-stimulated pp1 mRNA accumulation showed a lower threshold compared with insulin release (fig.1). In contrast, pp1 mRNA accumulation was further stimulated on raising medium glucose to 20 mM whereas insulin release, like biosynthesis [22], was saturated at 10 mM glucose ( fig.1).…”

“…Thus, like insulin biosynthesis [22], glucose-stimulated pp1 mRNA accumulation showed a lower threshold compared with insulin release (fig.1). In contrast, pp1 mRNA accumulation was further stimulated on raising medium glucose to 20 mM whereas insulin release, like biosynthesis [22], was saturated at 10 mM glucose ( fig.1). The observation that insulin biosynthesis persists after glucose stimulation has ceased [2] may be related to this continued accumulation of pp1 mRNA during periods of hyperglycaemic stress.…”

Glucose stimulates the biosynthesis of rat I and II insulin to an equal extent in isolated pancreatic islets

“…The specific and rapid stimulation of proinsulin/insulin biosynthesis by elevated extracellular glucose concentrations has been known for over 20 years [2][3][4]23]. The short-term (<2 h) regulation of insulin biosynthesis appears to be independent of net preproinsulin mRNA synthesis and thus arises at a translational level [24][25][26][27].…”

“…Its biosynthesis can be rapidly and specifically stimulated by glucose and certain other secretagogues [2][3][4].…”

Magnesium uptake by pancreatic islet cells is modulated by stimulators and inhibitors of the B‐cell function

“…Since 28Mg2+ uptake was increased by agents known to stimulate insulin biosynthesis [44] and decreased by agents (e.g. glucosamine, cationic amino acids) which do not stimulate insulin biosynthesis [44, 451, it is possible that a link exists between both phenomena.…”