Insulin Management

Gymnema is an herb native to southern and central India and has been widely used in ancient medicine. An Indian study administered 200 mg kg(-1) body weight of the alcoholic extract of Gymnema montanum for three weeks.¹ The extract significantly reduced blood glucose and increased plasma insulin, whereas the effect of 50 and 100 mg kg(-1) body weight was not significant. The alcoholic extract also resulted in decreased free radical formation in plasma of diabetic rats.

Another study administered an alcoholic extract of Gymnema sylvestre to rat islets of Langerhans and several pancreatic beta-cell lines.² The extract stimulated insulin release from HIT-T15, MIN6 and RINm5F beta-cells and from islets in the absence of any other stimulus, and G. sylvestre-stimulated insulin secretion was inhibited in the presence of 1 mM EGTA.

In two studies from Georgetown University Medical Center, Washington, chromium decreased SBP elevated by high-sucrose intake, bis(maltolato)oxovanadium (BMOV) overcame sucrose-induced elevation of SBP as well as some of the “genetic hypertension”, and G. sylvestre significantly lowered cholesterol, but neither lowered nor raised SBP.³ In the first study, spontaneously hypertensive rats (SHR) were fed either a starch, sugar or sugar diet containing chromium polynicotinate, BMOV or G. sylvestre. In a second study, SHR ingested diets containing different concentrations of BMOV. Compared to starch, SHR consuming sucrose showed a significant elevation of SBP within days that was maintained for the duration of study. Adding chromium polynicotinate to the sucrose diet prevented the sucrose-induced elevation of SBP for two weeks, but SBP rose significantly after that. BMOV at high concentrations overcame the sucrose-induced rise in SBP and decreased SBP below values seen in SHR eating the starch diet, but marked weight loss was noted. In the second study, BMOV SBP was still significantly decreased, even though SHR did not lose body weight early on. SHR consuming G. sylvestre showed no change or even elevated SBP. Hepatic thiobarbituric acid reacting substances (TBARS) formation, an estimate of lipid peroxidation, was decreased by chromium polynicotinate and BMOV, and renal TBARS by chromium polynicotinate. Circulating cholesterol concentrations were decreased in the SHR consuming G. sylvestre.

Vanadium is a soft metal that presents anti-diabetic characteristics. A Japanese in vivo study examined the anti-diabetic activity of poly(gamma-glutamic acid)oxovanadium(IV) complex (VO(gamma-pga) compared to vanadium(IV) oxide sulfate (VS) as a control.⁴ Both compounds were orally administered at doses of 5 to 10 mg (0.1-0.2 mmol) V kg(-1) body mass to the KKA(y) mice for 30 days. VO(gamma-pga) normalized the hyperglycemia within 21 days, whereas VS lowered the blood glucose concentration only by a small degree. In addition, the glucose intolerance, HbA(1c) level, hyperinsulinemia, hypercholesterolemia and hyperleptinemia were significantly improved in VO(gamma-pga)-treated KKA(y) mice compared with those treated with VS. A separate study found vanadium could exert its insulin sensitizing effects through the stimulation of adiponectin through a PKB-dependent transduction pathway.⁵

Alpha-lipoic acid (ALA) is a natural compound with antioxidant properties. French researchers said, “ALA scavenges hydroxyl radicals, hypochlorous acid and singlet oxygen. It may also exert antioxidant effects in biological systems through transitional metal chelation. A number of experimental as well as clinical studies point to the usefulness of ALA as a therapeutic agent for such diverse conditions as diabetes, atherosclerosis, insulin resistance, neuropathy, neurodegenerative diseases and ischemia-reperfusion injury.”⁶

A review published in Expert Opinion on Investigational Drugs noted, “ALA has been shown to cause weight loss, ameliorate insulin resistance and atherogenic dyslipidemia, as well as to lower blood pressure, all of these being components of the metabolic syndrome.”⁷

A study conducted at Emory University School of Medicine, Atlanta, randomized 58 subjects with the metabolic syndrome in a double blinded manner to 150 mg/d of irbesartan (n=14), 300 mg/d of lipoic acid (n=15), both irbesartan and lipoic acid (n=15), or matching placebo (n=14) for four weeks.⁸ After four weeks of therapy, endothelium-dependent flow-mediated vasodilation of the brachial artery was increased by 67 percent, 44 percent and 75 pecent in the irbesartan, lipoic acid and irbesartan plus lipoic acid groups, respectively, compared with the placebo group. Treatment with irbesartan and/or lipoic acid significantly reduced plasma levels of interleukin-6 and plasminogen activator-1, and decreased 8-isoprostane levels.

References on the next page...

References for "Insulin Management"

1. Ananthan R et al. “Antidiabetic effect of Gymnema montanum leaves: effect on lipid peroxidation induced oxidative stress in experimental diabetes” Pharmacol Res. 2003;48(6):551-6

2.      Persaud SJ et al. “Gymnema sylvestre stimulates insulin release in vitro by increased membrane permeability” J Endocrinol. 1999;163(2):207-12

3.      Preuss HG “Comparative effects of chromium, vanadium and gymnema sylvestre on sugar-induced blood pressure elevations in SHR” J Am Coll Nutr. 1998;17(2):116-23

4.      Karmaker S et al. “Amelioration of hyperglycemia and metabolic syndromes in type 2 diabetic KKA(y) mice by poly(gamma-glutamic acid)oxovanadium(IV) complex” ChemMedChem. 2007;2(11):1607-12

5.      Seale AP et al. “Vanadium and insulin increase adiponectin production in 3T3-L1 adipocytes” Pharmacol Res. 2006;54(1):30-8. Epub 2006 Mar 9

6.      Ghibu S et al. “An endogenous dithiol with antioxidant properties: Alpha-lipoic acid, potential uses in cardiovascular diseases” Ann Cardiol Angeiol (Paris). 2008;57(3):161-5. Epub 2008 Jun 4

7.      Pershadsingh HA “Alpha-lipoic acid: physiologic mechanisms and indications for the treatment of metabolic syndrome” Expert Opin Investig Drugs. 2007 Mar;16(3):291-302

8.      Sola S et al. “Irbesartan and lipoic acid improve endothelial function and reduce markers of inflammation in the metabolic syndrome: results of the Irbesartan and Lipoic Acid in Endothelial Dysfunction (ISLAND) study” Circulation. 2005;111(3):343-8. Epub 2005 Jan 17