The effect of sugars on (pro)insulin biosynthesis

Area of Science:

• Biochemistry
• Cell Biology
• Endocrinology

Background:

• Insulin and proinsulin biosynthesis are critical for glucose homeostasis.
• Understanding the regulation of insulin biosynthesis provides insights into metabolic diseases.
• Previous studies suggest glucose influences insulin release and synthesis.

Purpose of the Study:

• To investigate the effects of various carbohydrates and analogues on insulin and proinsulin biosynthesis in rat pancreatic islets.
• To explore the potential shared regulatory mechanisms between insulin release and biosynthesis.
• To elucidate the kinetics and thresholds of glucose-stimulated insulin and proinsulin synthesis.

Main Methods:

• Measurement of [4,5-(3H]leucine incorporation into insulin plus proinsulin ((pro)insulin) and total protein in rat pancreatic islets.
• Testing the effects of glucose, mannose, N-acetylglucosamine, inosine, dihydroxyacetone, and fructose on protein biosynthesis.
• Evaluating the inhibitory effects of mannoheptulose and phloretin on stimulated biosynthesis.

Main Results:

• Glucose, mannose, and N-acetylglucosamine preferentially stimulated (pro)insulin biosynthesis.
• Specific substrates like inosine and dihydroxyacetone also stimulated (pro)insulin biosynthesis.
• Fructose potentiated glucose- or mannose-induced stimulation; mannoheptulose and phloretin showed differential inhibitory effects.
• Caffeine and isobutylmethylxanthine did not affect glucose-stimulated (pro)insulin biosynthesis.

Conclusions:

• A common glucose-sensor mechanism may regulate both insulin release and biosynthesis.
• A 'substrate-site' model is proposed for the regulation of insulin and proinsulin synthesis.
• The threshold for stimulating biosynthesis is lower, and the response is slower, than for insulin release.