Dairy products and insulin resistance.
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Calcium↗
Biomedical subjects
Mark F McCarty
Publications and source records attributed to Mark F McCarty.
Incorporation of beta cell redifferentiation therapy into a lipoprivic strategy for reversing type 2 diabetes.
Type 2 diabetes (non-insulin-dependent diabetes mellitus, NIDDM), at least in the majority of patients characterized by insulin resistance and increased visceral fat, appears to be precipitated by the exposure of tissues to excessive levels of free fatty acids; this can contribute to the muscle insulin resistance, excessive hepatic gluconeogenesis, and beta cell dysfunction that collaborate to impair glycemic control. The resultant hyperglycemia, in turn, exacerbates the insulin resistance and beta cells dysfunction. The failure of glucose-stimulated insulin secretion (GSIS) in beta cells helps to sustain the elevations of serum glucose and free fatty acids, which in turn reinforce the failure of GSIS, possibly by inhibiting expression of the transcription factor IDX-1; NIDDM thus represents a vicious cycle that is not easily broken. A new strategy for achieving rapid loss of body fat - hepatothermic therapy (HT), an integrated approach involving exercise training, low-fat, low-glycemic-index food choices, and a supplementation program that promotes hepatic fatty acid oxidation - shows promise for alleviating the excessive fat exposure at the root of the diabetic syndrome, as well as the underlying insulin resistance syndrome responsible for increased macrovascular risk. However, when HT proves incapable of breaking the vicious cycle sustaining beta cell dysfunction, a supplementary strategy, beta cell redifferentiation therapy (BRT), may be required. BRT consists of a protocol in which near-normoglycemia is maintained for several weeks through use of intensive insulin therapy (e.g. artificial pancreas) or other effective measures, during which time beta cell GSIS can be expected to substantially recover owing to relief from glucolipotoxicity. Clinical experience demonstrates that this improved beta cell function, in certain cases, can persist for months or years after temporary BRT. A portion of the improved glycemic control achieved with very low calorie diets in NIDDM is reflective of improved GSIS, presumably consequent to a sustained reduction in diurnal glycemia. Long-lived analogs of glucagon-like peptide-1 (GLP-1) may find a key role in BRT; this incretin hormone not only potentiates GSIS, but also appears to increase the expression and activity of IDX-1 in beta cells, thus promoting beta cell redifferentiation. If HT is instituted prior to and following BRT to alleviate the FFA overexposure that initially precipitated the diabetic syndrome, it seems likely that the benefits of BRT will be conserved in the long term, thus enabling a reversal of NIDDM - in other words, maintenance of normoglycemia without medication. Since NIDDM is inherently preventable, its reversal should be the fundamental goal of diabetes therapy.
Cell Differentiation↗
Insulin's stimulation of endothelial superoxide generation may reflect up-regulation of isoprenyl transferase activity that promotes rac translocation.
Recent research demonstrates that statin drugs exert a number of favorable effects on endothelial function, independent of lipid modulation, that appear to be mediated by a partial inhibition of prenylation reactions. Statin-induced suppression of PKC-evoked superoxide production may be attributable to an inhibition of rac prenylation and thus translocation that impedes activation of the membrane-bound NAD(P)H oxidase. Conversely, it is now known that hyperinsulinemia up-regulates prenylation reactions by boosting the activities of isoprenyl transferases. In light of new evidence that hyperinsulinemia stimulates endothelial superoxide production via NAD(P)H oxidase, it is tempting to conclude that up-regulation of rac prenylation is at least partially responsible for this phenomenon. In patients afflicted with insulin resistance syndrome, this adverse impact of hyperinsulinemia may be exacerbated by an excessive free fatty acid flux that activates endothelial PKC - another stimulant of the NAD(P)H oxidase - while impeding insulin-mediated activation of nitric oxide synthase. The resulting imbalance of endothelial nitric oxide and superoxide production may be responsible for much of the excess vascular risk associated with this syndrome.
Endothelium↗
Favorable impact of a vegan diet with exercise on hemorheology: implications for control of diabetic neuropathy.
A little-noticed clinical report indicates that a low-fat, whole-food vegan diet, coupled with daily walking exercise, leads to rapid remission of neuropathic pain in the majority of type 2 diabetics expressing this complication. Concurrent marked improvements in glycemic control presumably contribute to this benefit, but are unlikely to be solely responsible. Consideration should be given to the possibility that improved blood rheology - decreased blood viscosity and increased blood filterability - plays a prominent role in mediating this effect. There is considerable evidence that neural hypoxia, secondary to impaired endoneurial microcirculatory perfusion, is a crucial etiologic factor in diabetic neuropathy; the unfavorable impact of diabetes on hemorheology would be expected to exacerbate endoneurial ischemia. Conversely, measures which improve blood fluidity would likely have a beneficial impact on diabetic neuropathy. There is indeed evidence that vegan diets, as well as exercise training, tend to decrease the viscosity of both whole blood and plasma; reductions in hematocrit and in fibrinogen may contribute to this effect. The fact that vegan diets decrease the white cell count is suggestive of an improvement in blood filterability as well; filterability improves with exercise training owing to an increase in erythrocyte deformability. Whether these measures influence the activation of leukocytes in diabetics - an important determinant of blood filterability - remains to be determined. There are various reasons for suspecting that a vegan diet can reduce risk for other major complications of diabetes - retinopathy, nephropathy, and macrovascular disease - independent of its tendency to improve glycemic control in type 2 patients. The vegan diet/exercise strategy represents a safe, 'low-tech' approach to managing diabetes that deserves far greater attention from medical researchers and practitioners.
Diabetic Nephropathies↗
Glucomannan minimizes the postprandial insulin surge: a potential adjuvant for hepatothermic therapy.
Glucomannan (GM) is differentiated from other soluble fibers by the extraordinarily high viscosity of GM solutions. Administration of 4-5g of GM with meals, blended into fluid or mixed with food, can slow carbohydrate absorption and dampen the postprandial insulin response by up to 50%. Controlled clinical studies document that GM can promote satiety and weight loss, lower LDL cholesterol, improve diabetic control, and correct constipation, with minimal if any side-effects. Rodent studies suggest that GM may have potential for decreasing cancer risk and possibly even slowing the ageing process. Hepatothermic therapy, a technique for achieving rapid loss of body fat by optimizing the liver's capacity for fat oxidation, can only achieve its optimal efficacy if diurnal insulin levels are kept low; ingestion of GM with meals will evidently be of benefit in this regard by moderating postprandial insulin surges.
Appetite↗
Pre-exercise administration of yohimbine may enhance the efficacy of exercise training as a fat loss strategy by boosting lipolysis.
The natural alpha-2 antagonist yohimbine promotes sympathetic activity by central as well as peripheral mechanisms, and yet in moderate doses dose not usually raise heart rate, increase blood pressure, or induce anxiety (in contrast to sympathomimetic drugs such as ephedrine). Administered prior to exercise, it boosts lipolysis and serum FFA levels both during and following exercise; blockade of adipocyte alpha-2 adrenoreceptors makes at least a modest contribution to this pro-lipolytic activity. These considerations suggest that pre-exercise administration of yohimbine will lower the respiratory quotient during and following exercise, thus promoting fat loss. Since yohimbine can potentiate postprandial insulin secretion, its bariatric benefits should be greatest if administered on a schedule that minimizes postprandial yohimbine activity. A possible synergism of yohimbine and caffeine should be explored. Pre-exercise yohimbine administration has the potential to down-regulate the lipoprotein lipase activity of visceral adipocytes, increase lipolysis in refractory gynoid fat depots, and improve the impaired lipolytic response to exercise in the elderly.
Adrenergic alpha-2 Receptor Antagonists↗
Vitamin D status and muscle strength.
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Aged↗