Maintenance of normal blood glucose levels depends on a complex interplay between
the insulin responsiveness of skeletal muscle and liver and glucose-stimulated
insulin secretion by pancreatic b cells. Defects in the former are responsible for insulin
resistance, and defects in the latter are responsible for progression to hyperglycemia.
Emerging evidence supports the potentially unifying hypothesis that both of these
prominent features of type 2 diabetes are caused by mitochondrial dysfunction.
Type 2 diabetes is the most common metabolic disease in the world. In the United States,
it is the leading cause of blindness, end-stage renal disease, and nontraumatic loss of limb,
with associated health care costs estimated to exceed $130 billion per year (1). Of even
greater concern, type 2 diabetes is rapidly becoming a global pandemic and is projected
to afflict more than 300 million individuals worldwide by the year 2025, with most of
the increase occurring in India and Asia (2). Although the primary cause of this disease
unknown, it is clear that insulin resistance plays an early role in its pathogenesis and
that defects in insulin secretion by pancreatic b cells are instrumental in the progression to
hyperglycemia. Here, we explore the potentially unifying hypothesis that these two prominent
features of type 2 diabetes are both attributable to defects in mitochondria, the organelles
that provide energy to the cell.
Role of Intracellular Fatty Acid
Metabolites in Insulin Resistance
Several lines of evidence indicate that insulin resistance is an early feature of type 2
diabetes. First, virtually all patients with type 2 diabetes are insulin-resistant, and prospective
studies have shown that this insulinresistant state develops 1 to 2 decades before
the onset of the disease (3–5). Second, insulin resistance in the offspring of parents
with type 2 diabetes is the best predictor for later development of the disease . Lastly,
perturbations that reduce insulin resistance prevent the development of diabetes .作者: play0219 時間: 05-2-26 22:18 標題: 回覆: CGA大戰 看類型吧~心眼太謎的話最後還是會麻煩到大大身上說QQ"
要在這裡發嗎??那我來搶第一ˊ0ˋ 加入我的最愛當中...
推推推~兔子加油._.a作者: dryade64752 時間: 05-2-26 22:46 標題: 回覆: CGA大戰 恩~心眼太迷的話真的會很頭痛@@
趕快搶好第2個位子作者: lilyrital 時間: 05-2-26 23:35 標題: 回覆: CGA大戰 搶第三
挺難猜的 改天問你= ="作者: peri 時間: 05-2-27 02:23 標題: 回覆: CGA大戰 Skeletal muscle and liver are the two key insulin-responsive organs responsible for maintaining
normal glucose homeostasis, and their transition to an insulin-resistant state accounts
for most of the alterations in glucose metabolism seen in patients with type 2 diabetes.
Before considering whether mitochondrial dysfunction contributes to the development of insulin
resistance in these organs, it is first important to understand the cellular mechanisms responsible
for insulin resistance. As discussed by Lazar , there is growing evidence that circulating
cytokines secreted by fat tissue can modulate the insulin responsiveness of liver
and muscle. However, fatty acids and/or intracellular fatty acid metabolites such as
fatty acyl coenzyme As (fatty acyl CoAs)
, diacylglycerol , or ceramides are also thought to play a critical role.
Over 40 years ago, Randle et al. demonstrated that fatty acids caused insulin resistance
in an in vitro rat muscle preparation, and they hypothesized that this occurred by a
substrate competition mechanism . According to his model, increased oxidation of
muscle fatty acids would produce increased levels of intracellular acetyl CoA and citrate,
which in turn would inhibit, respectively, two enzymes involved in glucose utilization,
