Metformin restores prohormone processing enzymes and normalizes aberrations in secretion of proinsulin and insulin in palmitate‐exposed human islets
Authors' conclusion
Metformin normalized proinsulin and insulin secretion after prolonged nutrient-overstimulation, coupled with normalization of the converting enzymes, in isolated islets. In adolescents with obesity, metformin treatment was associated with improved PI/I, which was coupled with improved glycaemic control.
Study context
- Population
- Isolated human pancreatic islets from seven donors cultured at 5.5 mmol/L glucose and 0.5 mmol/L palmitate for 12, 24 or 72 h, metformin (25 μmol/L) added after 12 h; adolescents with obesity treated with metforminislets from 7 donors
- Participants
- 5 / 14 / 7
- Comparison
- Metformin vs no metformin in palmitate-exposed human islets; adolescents with obesity before vs after metformin treatment
- Normal glucose tolerancen = 5reference
- Prediabetesn = 14
- T2DMn = 7
- Outcome
- Proinsulin and insulin secretion, PC1/3 and CPE expression in palmitate-exposed human islets
Methodological detailsin vitro human islets, clinical cohort of adolescents with obesity
- In vitro human islets
- Clinical cohort of adolescents with obesity
Main finding
As reported in the abstract
- Palmitate for 12 and 24 h increased proinsulin and insulin proportionally
- After 72 h, proinsulin but not insulin continued to increase, with reduced PC1/3 and carboxypeptidase E (CPE) expression
- Metformin normalized PC1/3 and CPE expression, and proinsulin and insulin secretion
Further findings
Fasting proinsulin and insulin before treatment, adolescents with obesity
- Fasting proinsulin and insulin higher with T2DM than with NGT
PI/I, 2-h glucose and HbA1c after metformin, adolescents with obesity · after metformin treatment
- PI/I reduced after metformin in T2DM and prediabetes, with reduced 2-h glucose and HbA1c
Original publication
Metformin restores prohormone processing enzymes and normalizes aberrations in secretion of proinsulin and insulin in palmitate‐exposed human islets. Diabetes Obes Metab. Published 11 September 2023. doi:10.
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