Control Signaling, Control and Prevent Diabetes and Glycosylation

Interesting article on glucose transit from diet through body.

Stevia, my sugar free additive, has not been associated with insulin resistance.  In fact it is associated with improved glucose tolerance testing.

Fructose was appropriately highlighted as a bad sweetener and food additive.

Finally, the importance of signaling as the path to improvement is the take home message and my current understanding of metabolic or energy health.  I would highlight particularly the ability of the low glycogen liver to block gluconeogenesis from glucagon signaling when blood glucose is already elevated.

Dad,  we have known for years that fasting 48 hours restores insulin sensitivity.  I believe that diabetics should do the following:

Eat a low glycemic diet or Mediterranean diet.

Intermittently fast, deplete liver glycogen stores.

High intensity exercise, fastest way to deplete muscle glycogen (and liver glycogen.)

Resistance train to increase lean muscle to store and use glycogen without high blood levels.

Increase BDNF from brain and endothelial cells to maximally use glucose as the brain uses 20% of the bodies glucose.  Low BDNF is associated with brain insulin resistance.

http://nopr.niscair.res.in/handle/123456789/33739

NISCAIR ONLINE PERIODICALS REPOSITORY (NOPR) : A glucose-centric perspective of hyperglycemia

Abstract:     Digestion of food in the intestines converts the compacted storage carbohydrates, starch and glycogen, to glucose. After each meal, a flux of glucose (>200 g) passes through the blood pool (4-6 g) in a short period of 2 h, keeping its concentration ideally in the range of 80-120 mg/100 mL. Tissue-specific glucose transporters (GLUTs) aid in the distribution of glucose to all tissues. The balance glucose after meeting the immediate energy needs is converted into glycogen and stored in liver (up to 100 g) and skeletal muscle (up to 300 g) for later use. High blood glucose gives the signal for increased release of insulin from pancreas. Insulin binds to insulin receptor on the plasma membrane and activates its autophosphorylation. This initiates the post-insulin-receptor signal cascade that accelerates synthesis of glycogen and triglyceride. Parallel control by phos-dephos and redox regulation of proteins exists for some of these steps. A major action of insulin is to inhibit gluconeogensis in the liver decreasing glucose output into blood. Cases with failed control of blood glucose have alarmingly increased since 1960 coinciding with changed life-styles and large scale food processing. Many of these turned out to be resistant to insulin, usually accompanied by dysfunctional glycogen storage. Glucose has an extended stay in blood at 8 mM and above and then indiscriminately adds on to surface protein-amino groups. Fructose in common sugar is 10-fold more active. This random glycation process interferes with the functions of many proteins (e.g., hemoglobin, eye lens proteins) and causes progressive damage to heart, kidneys, eyes and nerves.
    Some compounds are known to act as insulin mimics. Vanadium-peroxide complexes act at post-receptor level but are toxic. The fungus-derived 2,5-dihydroxybenzoquinone derivative is the first one known to act on the insulin receptor. The safe herbal products in use for centuries for glucose control have multiple active principles and targets. Some are effective in slowing formation of glucose in intestines by inhibiting α–glucosidases (e.g., salacia/saptarangi). Knowledge gained from French lilac on active guanidine group helped developing Metformin (1,1-dimethylbiguanide) one of the popular drugs in use. One strategy of keeping sugar content in diets in check is to use artificial sweeteners with no calories, no glucose or fructose and no effect on blood glucose (e.g., steviol, erythrytol). However, the three commonly used non-caloric artificial sweeteners, saccharin, sucralose and aspartame later developed glucose intolerance, the very condition they are expected to evade. Ideal way of keeping blood glucose under 6 mM and HbA1c, the glycation marker of hemoglobin, under 7% in blood is to correct the defects in signals that allow glucose flow into glycogen, still a difficult task with drugs and diets.