Insuline Resistance - Diabetes and Weight Problems

Selective insulin resistance

The recent emergence of the concept of selective insulin resistance, in which tissues become resistant to insulin’s effect on glucose transport but remain sensitive to its lipogenic effect, has reinvigorated the hypothesis that HI may be a primary cause of weight gain that leads to obesity and type 2 diabetes

Williams KJ, Wu X. Imbalanced insulin action in chronic over nutrition: clinical harm, molecular mechanisms, and a way forward. Atherosclerosis. 2016;247:225–282. doi: 10.1016/j.atherosclerosis.2016.02.004

A good review article. (Read by me again on 28 Oct 2020)

Insulin and Insulin Resistance

Clin Biochem Rev. 2005 May; 26(2): 19–39.
PMCID: PMC1204764, PMID: 16278749
Insulin and Insulin Resistance
Gisela Wilcox

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1204764/

Physiology of Insulin Secretion

Pancreatic β cells secrete 0.25–1.5 units of insulin per hour during the fasting (or basal) state, sufficient to enable glucose insulin-dependent entry into cells. This level prevents uncontrolled hydrolysis of triglycerides and will maintain  normal fasting blood glucose levels. Basal insulin secretion accounts for over 50% of total 24 hour insulin secretion.  Meal-related insulin secretion accounts for the remaining fraction of the total daily output. In healthy lean individuals circulating venous (or arterial) fasting insulin concentrations are about 3–15 mIU/L or 18–90 pmol/L. 

Insulin Secretion in Response to Stimuli

Response to Glucose

In healthy individuals glucose stimulated pancreatic secretion is biphasic. Intravenous administration of glucose is associated with a rapid “first phase” of insulin release within 1 minute, peaking at 3–5 minutes, and lasting about 10 minutes; the slower onset “second phase” of insulin secretion begins shortly after the glucose bolus  lasts the duration of the hyperglycaemia and is proportional to the glucose concentration immediately prior to the glucose administration. The first phase of insulin secretion represents release of insulin already synthesised and stored in secretory granules; the second phase represents secretion of both stored and newly synthesised insulin. Overall insulin secretion relates to the total dose of glucose and its rate of administration; maximal pancreatic response occurs with 20 g of glucose given intravenously over 3 minutes in humans.

In contrast to the reproducible pattern of insulin secretion in response to intravenous glucose, insulin secretion following oral glucose is much more variable. With an oral glucose load, gastric emptying and gastrointestinal motility affect glucose absorption, gastro-intestinal hormones and neural input associated with glucose ingestion modify the insulin response, and insulin secretion continues some time after glucose ingestion.

The Insulin Resistance Syndrome

The insulin resistance syndrome describes the cluster of abnormalities which occur more frequently in insulin resistant individuals. These include glucose intolerance, dyslipidaemia, endothelial dysfunction and elevated procoagulant factors, haemodynamic changes, elevated inflammatory markers, abnormal uric acid metabolism, increased ovarian testosterone secretion and sleep-disordered breathing. Clinical syndromes associated with insulin resistance include type-2 diabetes, cardiovascular disease, essential hypertension, polycystic ovary syndrome, non-alcoholic fatty liver disease, certain forms of cancer and sleep apnoea.


Metabolic Syndrome

It has been estimated that in the United States some 25% of adults have the metabolic syndrome. In addition to an underlying genetic predisposition to insulin resistance, physical inactivity and excess energy intake are considered the main risk factors, with an unknown contribution from other factors such as chronic stress and sleep deprivation.

Dyslipidaemia

The lipid abnormalities associated with insulin resistance affect all lipid fractions. They are characterised by elevated fasting triglyceride levels, elevated postprandial triglyceride-rich remnant lipoproteins, low HDL cholesterol, and small dense LDL particles.


Front Physiol. 2011; 2: 112.
Published online 2011 Dec 30. Prepublished online 2011 Nov 1. doi: 10.3389/fphys.2011.00112
PMCID: PMC3248697
PMID: 22232606

The Role of Skeletal Muscle Glycogen Breakdown for Regulation of Insulin Sensitivity by Exercise
Jørgen Jensen, Per Inge Rustad, Anders Jensen Kolnes, and Yu-Chiang Lai
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248697/

Hyperinsulinemia

Hyperinsulinemia: a Cause of Obesity?

Karel A. Erion1,2 and Barbara E. Corkeycorresponding author1

Curr Obes Rep. 2017; 6(2): 178–186.

The recent emergence of the concept of selective insulin resistance, in which tissues become resistant to insulin’s effect on glucose transport but remain sensitive to its lipogenic effect, has reinvigorated the hypothesis that HI may be a primary cause of weight gain that leads to obesity and type 2 diabetes

Williams KJ, Wu X. Imbalanced insulin action in chronic over nutrition: clinical harm, molecular mechanisms, and a way forward. Atherosclerosis. 2016;247:225–282. doi: 10.1016/j.atherosclerosis.2016.02.004

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487935/

Hyperinsulinemia: An Early Indicator of Metabolic Dysfunction 

Dylan D Thomas, Barbara E Corkey, Nawfal W Istfan, Caroline M Apovian

Journal of the Endocrine Society, Volume 3, Issue 9, September 2019, Pages 1727–1747, https://doi.org/10.1210/js.2019-00065

https://academic.oup.com/jes/article/3/9/1727/5537533

28 Oct 2020

13 Feb 2019