p38 Mitogen-Activated Protein Kinase: A Critical Node Linking Insulin Resistance and Cardiovascular Diseases in Type 2 Diabetes Mellitus

Abstract

Type 2 diabetes is associated with insulin resistance, endothelial dysfunction and accelerated atherosclerotic diseases. Though underlying mechanisms remain to be unraveled, p38 mitogen-activated protein kinase (MAPK) appears to play important roles in their pathogenesis. As a member of the MAPK family, it regulates the activities of many transcription factors and proteins/enzymes and thus has a wide-spectrum of biological effects. Patients with insulin resistance and/or type 2 diabetes have high levels of plasma free fatty acids, inflammatory cytokines, and/or glucose, and over-activation of the cardiovascular renin-angiotensin system, all are capable of activating p38 MAPK. p38 MAPK plays a central role in hepatic glucose and lipid metabolism, leading to increased hepatic glucose production and decreased hepatic lipogenesis. The roles of p38 MAPK in insulin-mediated glucose uptake in skeletal muscle and adipose tissue remain controversial. p38 MAPK also mediates inflammatory processes and cell apoptosis. Recent evidence suggests that p38 MAPK may be the key node linking cardiovascular insulin resistance, endothelial dysfunction and the pathogenesis of atherosclerotic diseases through its influences on monocytes/macrophages, vascular endothelial cells, and vascular smooth muscle cells in type 2 diabetes. In addition, p38 MAPK also contributes significantly to cardiac injury during ischemia-reperfusion.

<i><b>Bifidobacterium</b></i><b> species lower serum glucose, increase expressions of insulin signaling proteins, and improve adipokine profile in diabetic </b><b>mice </b>

“…A study by Tanaka et al indicated that IKKβ induces both insulin action and diabetes, by a mechanism involving defective secretion in response to inflammatory cytokines (32). Another study showed that p38 MAP kinase is related to insulin resistance (22). Therefore, the lack of effects of JNK, IKKβ and p38 MAP kinase in the current study may suggest that deleterious actions associated with diabetes do not appear in Bifidobacterium spp.…”

C-reactive protein impairs hepatic insulin sensitivity and insulin signaling in rats: Role of mitogen-activated protein kinases

“…2,45,46 p38 MAPK plays a key role in hepatic glucose metabolism, 13 and ERK1/2 activation stimulates IRS-1 Ser 612 phosphorylation and thereby inhibits insulin signaling. 47 Consistent with reported hCRP activation of p38 MAPK and ERK1/2 in endothelial cells and macrophages, 10,48 we found that hCRP increased phosphorylated p38 MAPK and ERK1/2 ex vivo in liver tissues and in vitro in hepatocytes.…”

“…13 Moreover, JNK and ERK1/2 stimulate serine phosphorylation of IRS-1, an important mechanism that inhibits IRS-1-mediated insulin signaling. 14,15 The potential effect of hCRP on these pathways linking to insulin sensitivity remains elusive.…”

Physiological and molecular responses to an acute bout of reduced-exertion high-intensity interval training (REHIT)

“…Potentially this subsequently places the myocyte in a transient state of osmotic stress (Haussinger 1996). Intriguingly, in various cell types osmotic swelling has previously been shown to independently activate various signalling cascades known to be involved in cellular remodelling (Haussinger 1996;Liu and Cao 2009). It is interesting to speculate whether this type of osmotic stress could be a mechanism of adaptation with HIT.…”