Many studies show during type-2 diabetes non insulin mediated glucose uptake will upregulate and represent a major part in the regulation of glucose homeostasis at normal condition also. Which are the main pathways other than the ampk pathway involved in non insulin mediated glucose uptake?
The .pdf link does not seem to work. Can you provide another Joel?
Regards, Jonas
Previous attachment - American Journal of Hypertension 10: 720-727, 1997.
The insulin independent glucose uptake may be due to a higher insulin independent GLUT4 translocation to plasma membrane of insulin sensitive tissues. See the attached publication.
Dear Paula, your Pdfs are not reachable! Would you please upload again?
One important mechanisms about it, is by the GLUT1. However, we can´t discarded the relevance of nitric oxide to inducer the expression of GLUT4 in muscle cells.
It is not only due to an increase in Glut4. There is a direct effect of NO on glucose uptake at the skeletal muscle, heart and kidney.
There is eveidence for two types of GLUT-4 transporters, a GLUT4IR - insulin regulatable and a GLUT-4EX or ER - exercise regulatable. The GLUT-4IR is located in adipocytes and myocytes, while the GLUT-4ER are located only in myocytes and are activated in response to exercise and glycogen depletion.
I am not familiar with the ampk pathway you are referring to, so should probably not answer.. but here is another thought. At least in skeletal muscle, contractions cause translocation of Glut4 receptors from the intracellular vesicles to the surface, much like insulin does. So muscle contractions increase absorbtion of glucose from blood stream via two additive mechanisms: somehow they increase insulin sensitivity (thought to be the major mechanism) and they increase glucose uptake via the non-insulin dependent pathway described as well.
I will have to research the mechanisms you outline, thanks for your question!
So insulin resistance can be overcome in muscle tissue, and from my point of view, must be avoided in other tissues by tight glycemic control.
We discussed the possible mechanisms in our previous article (Nishida et al, Diabetes 53: 315–320, 2004). Please see page 318, second paragraph of this paper.
The question; "What is the major mechanism for non-insulin mediated glucose uptake" suggests that insulin secretion is the major mechanism for GLUT4 glucose disposal. This is a fundamental flaw because the paper of Cline et al. demonstrated that the transmembrane glucose transport is the rate-controlling step in insulin-stimulated muscle glycogen synthesis in patients with type 2 diabetes mellitus [1]. They also found no difference in the interstitial-fluid insulin concentration during the steady-state of hyperinsulinemic clamp studies in these patients as compared with normal subjects, suggesting that the delivery of insulin is not responsible for the approximalely 80 percent lower rate of glucose infusion in the patients with type 2 diabetes compared with that of normal subjects.
All glucose transporters are required for faciliated glucose diffusion into cells [2]. These transporters have two features in common: (a) they facilitate net movement of glucose only in the thermodynamically favored direction (i.e. delta G
I came across this interesting issue only now, 2.5mo later, and just would like to add the comments presented by two clinical study big guns: Kenneth Zierler and Reubin Andres, who in fact both developed the forearm technique in the 50's, and were closely involved in the development of clamp method in the early 70's. In their paper in Diabetes 2002, they in a quite compelling way summarized their views on the issue of non-insulin-induced glucose uptake of skeletal muscle: http://diabetes.diabetesjournals.org/content/51/9/2698.short
Hypoxia is another way the cells consume more glucose, by the two Gluts and 4