Insulin signaling and its application.

The discovery of insulin in 1921 introduced a new branch of research into insulin activity and insulin resistance. Many discoveries in this field have been applied to diagnosing and treating diseases related to insulin resistance. In this mini-review, the authors attempt to synthesize the updated discoveries to unravel the related mechanisms and inform the development of novel applications. Firstly, we depict the insulin signaling pathway to explain the physiology of insulin action starting at the receptor sites of insulin and downstream the signaling of the insulin signaling pathway. Based on this, the next part will analyze the mechanisms of insulin resistance with two major provenances: the defects caused by receptors and the defects due to extra-receptor causes, but in this study, we focus on post-receptor causes. Finally, we discuss the recent applications including the diseases related to insulin resistance (obesity, cardiovascular disease, Alzheimer's disease, and cancer) and the potential treatment of those based on insulin resistance mechanisms.

Bifidobacterium species lower serum glucose, increase expressions of insulin signaling proteins, and improve adipokine profile in diabetic mice.

This study, using C57BL/6J mice with streptozotocin (STZ)-induced diabetes, aimed to determine whether Bifidobacterium species (spp.) both induces the expressions of proteins in the insulin signaling pathway and enhances the expressions of certain adipocytokines. The protein expressions of IκB kinase alpha (IKKα), IκB kinase beta (IKKß), nuclear factor-kappaB inhibitor alpha (IκBα), and the mitogen-activated protein kinase (MAPK) pathway were also investigated. Oral administration of Bifidobacterium spp. reduced blood glucose levels significantly and increased the protein expressions of insulin receptor beta, insulin receptor substrate 1, protein kinase B (Akt/PKB), IKKα, and IκBα. Extracellular-signal-regulated kinase 2 (ERK2) showed increased expression. Bifidobacterium spp. also induced the adiponectin expression and decreased both macrophage chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) expression. In addition, IKKß, c-Jun NH2-terminal kinase (JNK) and p38 MAP kinase expressions showed no significant changes in both groups. In conclusion, Bifidobacterium spp. may be the promising bacteria for treating diabetes.

Oral administration of Bifidobacterium spp. improves insulin resistance, induces adiponectin, and prevents inflammatory adipokine expressions.

The intestinal microbiome might be an important contributor to the development of type 2 diabetes. This study was designed to test the hypothesis that oral administration of Bifidobacterium species (spp.) (including B. longum, B. bifidum, B. infantis, and B. animalis) may both ameliorate insulin resistance and reduce the expressions of inflammatory adipocytokines. Male Swiss-Webster mice fed a high-fat diet with or without oral administration of Bifidobacterium spp. for 5 weeks were subjected to an insulin tolerance test and an oral glucose tolerance test. Plasma levels of glucose at 30, 60, 90 and 120 min after insulin injection or glucose administration were significantly lower in the Bifidobacterium spp. than in the control group (P < 0.05), showing the beneficial effect of oral administration on insulin resistance in obese Swiss mice. In addition, Bifidobacterium spp. increased the adiponectin mRNA level and decreased those of monocyte chemoattractant protein 1 and interleukin 6 in non-diabetic C57BL/6J mice fed a normal diet, indicating a molecular mechanism which may ameliorate the inflammatory state, thereby reducing insulin resistance. In conclusion, oral administration of Bifidobacterium spp. improves insulin resistance and glucose tolerance in obese mice by reducing inflammation, as it does in the lean state.