Tuesday, 29 November 2011

New GLP-1 stuff

Understanding the Cardiovascular Effects of Incretin.

Cardiovascular disease (CVD), a leading cause of death in patients with diabetes mellitus, has several pathogenic mechanisms that are well established. However, the traditional hypoglycemic agents do not have proven positive effects on macrovascular disease. Novel therapeutic agents target the incretin pathway including the glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) agonists and the dipeptidyl peptidase-4 inhibitors. The glucose-regulatory actions of these agents function by increasing insulin secretion and suppressing glucagon. They also act to increase weight loss not only by inhibiting gastric emptying, but also by reducing appetite.

Although GLP-1 and GLP-1R agonists have demonstrated beneficial effects on myocardium and vascular endothelium including coronary and peripheral mouse vessels, they also have anti-inflammatory and anti-atherogenic actions. These agents also have positive effects on the lipid profile and blood pressure. Although these cardioprotective actions seem to be beyond the effects of glucose control and weight loss, they are mediated through GLP-1R- or GLP-1R-independent actions of cleaved GLP-1 (9-36). Larger randomized controlled trials are necessary to elucidate the clinical promise of these beneficial CVD effects.

Combined stimulation of glucagon-like peptide-1 receptor and inhibition of cannabinoid CB1 receptor act synergistically to reduce food intake and body weight in the rat.

Acute activation of central Glp1 receptors enhances hepatic insulin action and insulin secretion in high fat-fed, insulin resistant mice.

The Gut Hormones PYY(3-36) and GLP-1(7-36 amide) Reduce Food Intake and Modulate Brain Activity in Appetite Centers in Humans.

Ketogenic Diet to help supress cancer?


Couldnt help, had to post this here.
Over the last years, evidence has accumulated suggesting that by systematically reducing the
amount of dietary carbohydrates (CHO) one could suppress, or at least delay, the emergence
of cancer, and that proliferation of already existing tumor cells could be slowed down. This
hypothesis is supported by the association between modern chronic diseases like the
metabolic syndrome and the risk of developing or dying from cancer. CHOs or glucose, to
which more complex carbohydrates are ultimately digested, can have direct and indirect
effects on tumor cell proliferation: first, contrary to normal cells, most malignant cells depend
on steady glucose availability in the blood for their energy and biomass generating demands
and are not able to metabolize significant amounts of fatty acids or ketone bodies due to
mitochondrial dysfunction. Second, high insulin and insulin-like growth factor (IGF)-1 levels
resulting from chronic ingestion of CHO-rich Western diet meals, can directly promote tumor
cell proliferation via the insulin/IGF-1 signaling pathway. Third, ketone bodies that are
elevated when insulin and blood glucose levels are low, have been found to negatively affect
proliferation of different malignant cells in vitro or not to be usable by tumor cells for
metabolic demands, and a multitude of mouse models have shown anti-tumorigenic properties
of very low-CHO ketogenic diets. In addition, many cancer patients exhibit an altered glucose
metabolism characterized by insulin resistance and may profit from an increased protein and
fat intake.
In this review, we address the possible beneficial effects of low CHO diets on cancer
prevention and treatment. Emphasis will be placed on the role of insulin and IGF-1 signaling
in tumorigenesis as well as altered dietary needs of cancer patients.