The Presence, Origins and Potential Role of Bi-hormonal Endocrine Cells Within the Pancreatic Islets of Langerhans
Bibliographic record
Abstract
The pancreatic islets of Langerhans contain a minority of endocrine cells that contain more than one hormone: predominantly combinations of glucagon, insulin and somatostatin. A recent paper from our laboratory examined the ontogeny of such cells in the human pancreas and found that they persisted throughout the lifespan but altered in relative abundance with age. Glucagon/insulin bi-hormonal cell number significantly increased with age whilst insulin/somatostatin and glucagon/somatostatin cells significantly decreased. Building on that study here we explore the possible origins and physiological role of bi-hormonal cells within the endocrine pancreas. During pancreas development in utero mono-hormonal endocrine cell lineages are defined by distinct signatures of transcription factor expression. Insufficient or inappropriately timed expression in sub-populations of endocrine cell progenitors may fail to suppress genes normally restricted to other endocrine cell types, resulting in residual populations of bi-hormonal cells. These have been identified postnatally by single cell transcriptomic or proteomic analysis and do not appear to have a metabolic role distinct from that of mono-hormonal cells. However, during hyperglycemic stress bi-hormonal cell sub-populations can proliferate and transdifferentiate into new beta-cells capable of glucose-stimulated insulin release. Transdifferentiation is reversible and in both type 1 and 2 diabetes some beta-cells can dedifferentiate to form hormone-null cells or alpha-cells. Thus, current evidence suggests that diverse phenotypic pools of endocrine cell phenotypes are retained within the islets into adult life that can undergo lineage changes in response to metabolic demand. There is preliminary evidence that these pathways can be therapeutically manipulated.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".