Prolonged insulin-induced hypoglycaemia reduces ß-cell activity rather than number in pancreatic islets in non-diabetic rats
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Prolonged insulin-induced hypoglycaemia reduces ß-cell activity rather than number in pancreatic islets in non-diabetic rats. / Jensen, Vivi F.H.; Mølck, Anne Marie; Nowak, Jette; Fels, Johannes J.; Lykkesfeldt, Jens; Bøgh, Ingrid B.
In: Scientific Reports, Vol. 12, 14113, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Prolonged insulin-induced hypoglycaemia reduces ß-cell activity rather than number in pancreatic islets in non-diabetic rats
AU - Jensen, Vivi F.H.
AU - Mølck, Anne Marie
AU - Nowak, Jette
AU - Fels, Johannes J.
AU - Lykkesfeldt, Jens
AU - Bøgh, Ingrid B.
N1 - Publisher Copyright: © 2022, The Author(s).
PY - 2022
Y1 - 2022
N2 - Pancreatic β-cells have an extraordinary ability to adapt to acute fluctuations in glucose levels by rapid changing insulin production to meet metabolic needs. Although acute changes have been characterised, effects of prolonged metabolic stress on β-cell dynamics are still unclear. Here, the aim was to investigate pancreatic β-cell dynamics and function during and after prolonged hypoglycaemia. Hypoglycaemia was induced in male and female rats by infusion of human insulin for 8 weeks, followed by a 4-week infusion-free recovery period. Animals were euthanized after 4 or 8 weeks of infusion, and either 2 days and 4 weeks after infusion-stop. Total volumes of pancreatic islets and β-cell nuclei, islet insulin and glucagon content, and plasma c-peptide levels were quantified. Prolonged hypoglycaemia reduced c-peptide levels, islet volume and almost depleted islet insulin. Relative β-cell nuclei: total pancreas volume decreased, while being unchanged relative to islet volume. Glucagon: total pancreas volume decreased during hypoglycaemia, whereas glucagon: islet volume increased. Within two days after infusion-stop, plasma glucose and c-peptide levels normalised and all remaining parameters were fully reversed after 4 weeks. In conclusion, our findings indicate that prolonged hypoglycaemia inactivates β-cells, which can rapidly be reactivated when needed, demonstrating the high plasticity of β-cells even following prolonged suppression.
AB - Pancreatic β-cells have an extraordinary ability to adapt to acute fluctuations in glucose levels by rapid changing insulin production to meet metabolic needs. Although acute changes have been characterised, effects of prolonged metabolic stress on β-cell dynamics are still unclear. Here, the aim was to investigate pancreatic β-cell dynamics and function during and after prolonged hypoglycaemia. Hypoglycaemia was induced in male and female rats by infusion of human insulin for 8 weeks, followed by a 4-week infusion-free recovery period. Animals were euthanized after 4 or 8 weeks of infusion, and either 2 days and 4 weeks after infusion-stop. Total volumes of pancreatic islets and β-cell nuclei, islet insulin and glucagon content, and plasma c-peptide levels were quantified. Prolonged hypoglycaemia reduced c-peptide levels, islet volume and almost depleted islet insulin. Relative β-cell nuclei: total pancreas volume decreased, while being unchanged relative to islet volume. Glucagon: total pancreas volume decreased during hypoglycaemia, whereas glucagon: islet volume increased. Within two days after infusion-stop, plasma glucose and c-peptide levels normalised and all remaining parameters were fully reversed after 4 weeks. In conclusion, our findings indicate that prolonged hypoglycaemia inactivates β-cells, which can rapidly be reactivated when needed, demonstrating the high plasticity of β-cells even following prolonged suppression.
U2 - 10.1038/s41598-022-18398-z
DO - 10.1038/s41598-022-18398-z
M3 - Journal article
C2 - 35982111
AN - SCOPUS:85136145478
VL - 12
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 14113
ER -
ID: 319163903