Accumulation of Cholesterol Linked with T2 Diabetes

[dina1957]

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Accumulation of Cholesterol Linked With Type 2 Diabetes
Date: Tuesday, February 27 ~ 13:11:08 CST
Topic: DIC Newsletter Issue 353

An international team of scientists have discovered a possible link between accumulation of cholesterol –lipid toxicity and type 2 diabetes.

Type 2 diabetes is defined by two things. One is insulin resistance, and the other is reduced insulin production. The second is caused by reduction in insulin release by "beta cells" in the pancreas. Why this happens is poorly understood; however, it has been suggested that the build up of toxic lipids in the cells could be a reason.

Using mice, scientists showed that pancreatic beta cells, responsible for insulin release, begin to malfunction when their cholesterol levels build up.

They examined the role of a molecular transporter called "ATP-binding cassette transporter A1" (ABCA1). ABCA1 is important for "cholesterol homeostasis" which regulates cholesterol levels in cells. It also affects insulin secretion in pancreatic beta cells. The scientists used genetically engineered mice and switched off their ABCA1 genes.

They found that these mice had normal insulin sensitivity, but lower levels of insulin secretion and significantly impaired glucose tolerance, displaying one of the classic symptoms of type 2 diabetes. They effectively became diabetic.

When they examined the pancreas of the mice, isolated and tested the cells "in vitro", they found the cholesterol homeostasis was different to normal as was the secretion of insulin. They also found a significant accumulation of cholesterol in the beta cells.

Cholesterol plays a number of roles in the human body, and one of these is to keep cell membranes healthy so they allow the right chemicals to pass in and out of the cells. However, the levels of cholesterol have to be regulated precisely. n the case of the beta cells, if the cholesterol levels accumulate, they interfere with the secretion of insulin. This is the one of the possible explanations, say the scientists on this study.

However, there are competing theories. One is that amylin, one of the peptide hormones produced by the beta cells and secreted at the same time as insulin, builds up and interferes with insulin release. According to Dr Michael Hayden, in whose lab the study was conducted, more studies will be done this year to see if cholesterol regulation problems also occur in humans with type 2 diabetes.

"Beta-cell ABCA1 influences insulin secretion, glucose homeostasis and response to thiazolidinedione treatment." Liam R Brunham, Janine K Kruit, Terry D Pape, Jenelle M Timmins, Anne Q Reuwer, Zainisha Vasanji, Brad J Marsh, Brian Rodrigues, James D Johnson, John S Parks, C Bruce Verchere and Michael R Hayden Nature Medicine Published online: 18 February 2007 doi:10.1038/nm1546

Click here for Abstract. (http://www.nature.com/nm/journal/vaop/ncurrent/abs/nm1546.html) ===========================

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[Markm]

This confused me:
Type 2 diabetes is defined by ..... reduced insulin production .... caused by reduction in insulin release by "beta cells" in the pancreas. Why this happens is poorly understood
.... I thought this was well understood - beta cells become exhausted by the excessive production of insulin, which is required because of insulin resistance. Blaming falling insulin production on choleterol sounds like a really big stretch to me.

Mark

[dina1957]

This confused me:

.... I thought this was well understood - beta cells become exhausted by the excessive production of insulin, which is required because of insulin resistance. Blaming falling insulin production on choleterol sounds like a really big stretch to me.

Mark
I never thought it is one single cause. otherwise, how do you explain some when morbidly obese folks have no diabetes. Obviously, their bodies makes large amount of insulin so they gain weight easily and have hard time to lose it. But somehow, their pancrease does not get exhausted from massive amount of insulin? What, they have ironclad pancrease or may be greater number of betta-cells to begin with? it seem same stretch to me as exercise makes heart beat faster, so if you do it daily - your heart will get exhausted and stop beating? Or eat lots of fat - and exhaust your liver and gall bladder, breath more often - exaust your lungs, and then we should not drink lots of water either, to preserve kidneys. Oh, and don't use your brain too much, it may exhaust your gray matter and burn brain cells. ;)
Ok, on a serious side, why pancrease fails in some ppl with slightly elevated insulin level and does not in others with much higher? Why beta cells stop manufacture, other organs do not fit into this approach? How many diabetics had their fasting insilin and c-peptide tested? Most T2 have more than needed insulin, but may be it is not good quality?
Problem with diabetes is not only pancreatic cell burnout, it is more complicated. They just trying different theories, I believe T2 diabetes is multifactoral disorder, not just exhausted pancrease and massive amount of insulin.

Just some thoughts.