Bibliographic record
Abstract
The perspective presented here is a working hypothesis suggesting a new paradigm for insulin resistance where, analogous to the cause of type 1 diabetes being attributed to lack of insulin, type 2 diabetes is due to lack of action of a hepatic insulin sensitizing substance (HISS). In both cases, the major metabolic dysfunction is with post-meal nutrient processing. In the immediate postprandial state, insulin causes the release of the putative hormone, HISS, from the liver. HISS stimulates glucose uptake in skeletal muscle. The hepatic parasympathetic nerves determine, in a permissive manner, the ability of insulin to cause HISS release maximally in the postprandial state. HISS release in response to insulin is progressively reduced with fasting. The glucose disposal effect of insulin in the fed state is decreased by approximately 55% by blocking HISS release. HISS release is blocked by fasting, surgical parasympathetic denervation of the liver, blockade of hepatic cholinergic muscarinic receptors, blockade of hepatic nitric oxide production, or blockade of hepatic cyclooxygenase, and results in a condition referred to as HISS-dependent insulin resistance (HDIR). HDIR is physiologically and appropriately produced in the fasted state and, pathologically, in chronic liver disease, sucrose fed, fetal alcohol exposed, spontaneously hypertensive, and aging rats. Therapeutic approaches to correct the metabolic imbalance in processing the meal nutrients that occur in type 2 diabetes can be approached through this paradigm.
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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 | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.002 | 0.011 |
| Scholarly communication | 0.005 | 0.008 |
| Open science | 0.002 | 0.004 |
| Research integrity | 0.005 | 0.008 |
| Insufficient payload (model declined to judge) | 0.009 | 0.002 |
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".