PT  - JOURNAL ARTICLE
AU  - Manawa Diwekar-Joshi
AU  - Milind Watve
TI  - Does insulin signalling decide glucose levels in the fasting steady state?
AID  - 10.1101/553016
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 553016
4099  - http://biorxiv.org/content/early/2019/07/16/553016.short
4100  - http://biorxiv.org/content/early/2019/07/16/553016.full
AB  - Recent work has suggested that altered insulin signalling may not be central to the pathophysiology of type 2 diabetes as classically believed. We critically re-examine the role of insulin in glucose homeostasis using five different approaches (i) systematic review and meta-analysis of tissue specific insulin receptor knock-outs, (ii) systematic review and meta-analysis of insulin suppression and insulin enhancement experiments, (iii) differentiating steady-state and post-meal state glucose levels in streptozotocin treated rats in primary experiments (iv) mathematical and theoretical considerations and (v) glucose insulin relationship in human epidemiological data. All the approaches converge on the inference that although insulin action is hastens the return to a steady-state after a glucose load, there is no evidence that insulin action determines the steady-state level of glucose. The inability to differentiate steady state causality from perturbed state causality has led to misinterpretation of the evidence for the role of insulin in glucose regulation.