Rachek LI: Free fatty acids and skeletal muscle insulin resistance.
Prog Mol Biol Transl Sci. 2014;121:267-92. doi: 10.1016/B978-0-12-800101-1.00008-9
Krista's reference relates to LDL receptor metabolism so don't think that answers the question. Birgitte's article looks like it might speak to the various issues being considered but I only have access to the abstract at present (which only tells me what the article will tell me). It makes physiologic sense however that when lipids are prevalent in the bloodstream, they will be used preferentially as fuel and will signal the cells to reduce their glucose transport and metabolism thus resulting in insulin resistance. Should be a straightforward feedback loop.
See if this helps. Also look at the references listed at the end of this article.
Samuel VT, Petersen KF, Shulman GI. Lipid-induced insulin resistance: unravelling the mechanism. Lancet. 2010 Jun 26;375(9733):2267-77.
¨Lipids impaired insulin-stimulated glucose use by muscles through inhibition of glycolysis at key points. However, work over the past two decades has shown that lipid-induced insulin resistance in skeletal muscle stems from defects in insulin-stimulated glucose transport activity. The steatotic liver is also resistant to insulin in terms of inhibition of hepatic glucose production and stimulation of glycogen synthesis. In muscle and liver, the intracellular accumulation of lipids-namely, diacylglycerol-triggers activation of novel protein kinases C with subsequent impairments in insulin signalling. This unifying hypothesis accounts for the mechanism of insulin resistance in obesity, type 2 diabetes, lipodystrophy, and ageing; and the insulin-sensitising effects of thiazolidinediones¨
I hope you find it useful!
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995547/pdf/nihms250988.pdf
Afonso et al British J Nutrition 2010, 104, 1450-1459 showed that a high fat diet caused reduction of meal-induced insulin sensitization (MIS) that progressed with duration of the diet and correlated with obesity. MIS is seen as a dramatic potentiation of the hypoglycemic effect of insulin pulses after a meal and is accounted for by a hepatic insulin sensitizing substance (HISS) released from the liver in response to insulin, but only in the presence of 2 feeding signals, hepatic parasympathetic nerves and elevated hepatic GSH levels. HISS acts selectively on skeletal muscle, heart and kidney to form glycogen, and results in the majority of glucose sequestration. Absence of HISS action results in absence of MIS (AMIS), which results in postprandial hyperglycemia and increased requirement for insulin. The lipogenic action of insulin results in a shift of storage of nutrient energy from muscle to fat. AMIS for one meal results in elevated postprandial glucose, insulin, lipids and free radicals. Chronic AMIS results in an AMIS syndrome that has progressive adiposity as an early component. A recent review discusses related work ( Chowdhury et al Can. J. Physiol. Pharmacol. 91: 91-100 2013.
Β-cells in high glucose itself induce the production of IL-1β and it has been shown to cause β-cell death and progressive loss of β-cells (1).
In pancreatic islets, high glucose concentrations increases islets cellular metabolic activity, these lead to increase reactive oxygen species (ROS), it also triggers the activation of NLRP3 inflammasome and caspase 1 and consequently is achieved to mature IL-1β production (1, 2).
Also the presence of free fatty acids increases glucose-induced β-cell-derived IL-1β (3) and the studies showing that excessive nutrition and obesity-induced metabolic disturbances resulting external pancreatic storage of oil deposition contribute to β-cell failure (4).
1. PubMed PMID: 12235117.
2. PubMed PMID: 20023662.
3. PubMed PMID: 21523780.
4. PubMed PMID: 21109192.
It's determined that caspase-1-dependent cytokines (particularly IL-1β and IL-18) induce inflammation in obesity and lead to insulin resistance and it may have important and probably a causative role in this situation.
PMID: 21109192 and 21217695.
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I suggest you also look at the following articles:
PubMed PMID: 24854413 and PubMed PMID: 24798950.
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