Biochemical adaptations of mammalian hibernation: exploring squirrels as a perspective model for naturally induced reversible insulin resistance

An important disease among human metabolic disorders is type 2 diabetes mellitus. This disorder involves multiple physiological defects that result from high blood glucose content and eventually lead to the onset of insulin resistance. The combination of insulin resistance, increased glucose production, and decreased insulin secretion creates a diabetic metabolic environment that leads to a lifetime of management. Appropriate models are critical for the success of research. As such, a unique model providing insight into the mechanisms of reversible insulin resistance is mammalian hibernation. Hibernators, such as ground squirrels and bats, are excellent examples of animals exhibiting reversible insulin resistance, for which a rapid increase in body weight is required prior to entry into dormancy. Hibernator studies have shown differential regulation of specific molecular pathways involved in reversible resistance to insulin. The present review focuses on this growing area of research and the molecular mechanisms that regulate glucose homeostasis, and explores the roles of the Akt signaling pathway during hibernation. Here, we propose a link between hibernation, a well-documented response to periods of environmental stress, and reversible insulin resistance, potentially facilitated by key alterations in the Akt signaling network, PPAR-γ/PGC-1α regulation, and non-coding RNA expression. Coincidentally, many of the same pathways are frequently found to be dysregulated during insulin resistance in human type 2 diabetes. Hence, the molecular networks that may regulate reversible insulin resistance in hibernating mammals represent a novel approach by providing insight into medical treatment of insulin resistance in humans.

Effects of gastric cancer cells on lymphocyte proliferation.

Lack of lymphocyte infiltration into gastric cancer tissue appears to be an ominous prognostic indicator. The effects of gastric cancer cells on PHA-induced lymphocyte proliferation were studied. Peripheral lymphocytes were co-cultured for 72 hours with either gastric cancer cells or normal mucosal cells. Pairs of cancerous and normal mucosal cells from stomachs of eight patients, were separately co-cultured with peripheral lymphocytes either from patients or from normal volunteers. The degree of PHA-induced lymphocyte proliferation was measured by 3H-thymidine incorporation. The lymphocyte proliferation was inhibited by the presence of either gastric cancerous or normal mucosal cells in a dose-related manner. The lymphocytes from the normals proliferated twice as much as did the lymphocytes from the patients. The isotope incorporation occurred in lymphocytes rather than in gastric cells since the later incorporated insignificant amounts of isotope. There was no difference between gastric cancerous or normal mucosal cells inhibiting the proliferation of either normal or patients' lymphocytes (p greater than 0.05). In conclusion, gastric cancerous cells (up to 10(6)/ml) have no enhanced inhibition on lymphocyte proliferation when compared with normal gastric mucosal cells.

Alterations of humoral immunity in patients with gastric cancer.

For better understanding of the alterations of humoral immunity in gastric cancer patients, IgG, IgA, IgM, complement C3, C4, CH50, natural antibody (isohemagglutinin-IgM class), ESR, CRP, albumin and globulin were quantitated in sera taken preoperatively from 81 patients with gastric cancer and from 29 control patients with hernia. The results from patients with gastric cancer were grouped according to pTNM staging (including stage I + II, III, and IV). Serum globulin and IgG levels in all stages of cancer patients were significantly lower than that of the controls (p less than 0.05). The CRP and ESR levels in stage III and IV cancer patients were significantly higher (p less than 0.05). There was no difference between cancer and hernia patient groups in IgA, IgM, isohemagglutinin-IgM class, C3, C4, CH50, albumin, WBC and total lymphocyte counts. In conclusion, the significant changes in humoral immunity in patients with gastric cancer include: (1) decrease in serum IgG and globulin levels, and (2) increased levels of acute phase reactants (ESR, CRP). These results imply that patients with gastric cancer have lower acquired humoral immunity and have acute phase reactions.