In pancreatic islets from type 2 diabetes patients, the dampened circadian oscillators lead to reduced insulin and glucagon exocytosis.
Level 5 - mechanism / opinion, no new human data
Ex vivo laboratory study on isolated human pancreatic tissue
PubMed 31964806 · doi:10.1073/pnas.1916539117
What was done
Researchers analyzed molecular circadian clock function in human pancreatic alpha- and beta-cells from non-diabetic donors and donors with type 2 diabetes (T2D) across population, single-islet, and single-cell levels. They evaluated hormone granule docking and exocytosis, and tested whether the RORα/γ agonist nobiletin could alter clock amplitude and insulin secretion in T2D islets.
What was found
The abstract reports directional and qualitative findings without specific numerical values, confidence intervals, or sample sizes. Islets from T2D donors exhibited decreased circadian amplitude and reduced in vitro synchronization capacity compared to non-diabetic controls. Attenuated islet clocks were linked to impaired docking and exocytosis of both insulin and glucagon granules. Application of nobiletin enhanced circadian amplitude and increased insulin secretion in T2D islets.
Why it matters
This work identifies cell-autonomous circadian oscillator impairment in human diabetic islets as a contributor to defective insulin and glucagon release, pointing to clock-modulating compounds as potential therapeutic targets.
Limits
The abstract provides no quantitative data, donor numbers, or demographic and clinical characteristics. Results are restricted to ex vivo tissue preparations and in vitro pharmacological manipulation, which cannot account for in vivo systemic, neural, or hormonal rhythms.
Cited by
- supports The pancreas has an endogenous clock that causes it to secrete more insulin in the morning and first half of the day than in the second half of the day.