Abnormal Expression of Pancreatic Islet Exocytotic Soluble<i>N</i>-Ethylmaleimide-Sensitive Factor Attachment Protein Receptors in Goto-Kakizaki Rats Is Partially Restored by Phlorizin Treatment and Accentuated by High Glucose Treatment
Bibliographic record
Abstract
The role of glucotoxicity in dysregulation of islet exocytotic soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex proteins and insulin response was explored in the hyperglycemic Goto-Kakizaki (GK) rat. Syntaxin-1A and vesicle-associated membrane protein isoform 2, which drive insulin granule exocytotic fusion, and the associated nSec1, which modulates the SNARE complex assembly, were diminished in GK pancreatic islets to approximately 40% of the levels in control Wistar rat islets. Phlorizin treatment (12 d) induced normoglycemic control in GK rats, resulting in partial restoration of the insulin response to glucose. Furthermore, islet SNARE complex and nSec1 proteins increased by about 40%. Phlorizin treatment did not affect levels of islet SNARE proteins in controls or on the same SNARE complex proteins in GK rat brain. To examine the role of hyperglycemia per se, GK and control rat islets were exposed for 5 d in culture to 5.5 and 16.7 mM glucose. High glucose treatment greatly increased the levels of synaptosomal-associated membrane protein of 25 kDa and, less markedly, the levels of syntaxin-1A and nSec1 in control islets more than in GK rat islets, whereas levels were reduced in both. This was accompanied by sustained impairment of the insulin response to glucose in GK islets and a normal response in control islets. Thus, GK islets demonstrate dysregulation of SNARE protein expression, and their compensatory increase by high glucose exposure is abrogated. Conversely, normoglycemic control results in partial replenishment of these critical components of the insulin exocytotic machinery and improvement in the insulin response. We propose that dysregulation of SNARE proteins is an important mechanism behind glucotoxicity-mediated impairment of the insulin response to glucose.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".