A procyanidin type A trimer from cinnamon extract attenuates glial cell swelling and the reduction in glutamate uptake following ischemia-like injury in vitro.

Dietary polyphenols exert neuroprotective effects in ischemic injury. The protective effects of a procyanidin type A trimer (trimer 1) isolated from a water soluble cinnamon extract (CE) were investigated on key features of ischemic injury, including cell swelling, increased free radical production, increased intracellular calcium ([Ca(2+)](i)), mitochondrial dysfunction, and the reduction in glutamate uptake. Astrocyte (glial) swelling is a major component of cytotoxic brain edema in ischemia and, along with vasogenic edema, may contribute to increased intracranial pressure, brain herniation, and additional ischemic injuries. C6 glial cultures were exposed to oxygen-glucose deprivation (OGD) for 5 h, and cell swelling was determined at 90 min after the end of OGD. OGD-induced increases in glial swelling were significantly blocked by trimer 1, but not by the major nonpolyphenol fractions of CE including cinnamaldehyde and coumarin. Increased free radical production, a contributing factor in cell swelling following ischemic injury, was also significantly reduced by trimer 1. Mitochondrial dysfunction, another key feature of ischemic injury, is hypothesized to contribute to glial swelling. Depolarization of the inner mitochondrial membrane potential (ΔΨ(m)) was assessed using a fluorescent dye (tetramethylrhodamine ethyl ester [TMRE]), and was significantly attenuated by trimer 1 as was OGD-induced increased [Ca(2+)](i). Taken together with our previous observation that blockers of [Ca(2+)](i) reduce cell swelling, our results indicate that trimer 1 may attenuate cell swelling by regulating [Ca(2+)](i). Trimer 1 also significantly attenuated the OGD-induced decrease in glutamate uptake. In addition, cyclosporin A, a blocker of the mitochondrial permeability pore (mPT), but not FK506 (that does not block the mPT), reduced the OGD-induced decline in glutamate uptake indicating a role of the mPT in such effects. Thus, the effects of trimer 1 in attenuating the reduction in glutamate uptake are likely mediated through their action on the mitochondria.

Cinnamon extract regulates plasma levels of adipose-derived factors and expression of multiple genes related to carbohydrate metabolism and lipogenesis in adipose tissue of fructose-fed rats.

We reported earlier that dietary cinnamon extract (CE) improves systemic insulin sensitivity and dyslipidemia by enhancing insulin signaling. In the present study, we have examined the effects of CE on several biomarkers including plasma levels of adipose-derived adipokines, and the potential molecular mechanisms of CE in epididymal adipose tissue (EAT). In Wistar rats fed a high-fructose diet (HFD) to induce insulin resistance, supplementation with a CE (Cinnulin PF, 50 mg/kg daily) for 8 weeks reduced blood glucose, plasma insulin, triglycerides, total cholesterol, chylomicron-apoB48, VLDL-apoB100, and soluble CD36. CE also inhibited plasma retinol binding protein 4 (RBP4) and fatty acid binding protein 4 (FABP4) levels. CE-induced increases in plasma adiponectin were not significant. CE did not affect food intake, bodyweight, and EAT weight. In EAT, there were increases in the insulin receptor ( IR) and IR substrate 2 ( IRS2) mRNA, but CE-induced increases in mRNA expression of IRS1, phosphoinositide-3-kinase, AKT1, glucose transporters 1 and 4 , and glycogen synthase 1 expression and decreased trends in mRNA expression of glycogen synthase kinase 3beta were not statistically significant. CE also enhanced the mRNA levels of ADIPOQ, and inhibited sterol regulatory element binding protein-1c mRNA levels. mRNA and protein levels of fatty acid synthase and FABP4 were inhibited by CE and RBP4, and CD36 protein levels were also decreased by CE. These results suggest that CE effectively ameliorates circulating levels of adipokines partially mediated via regulation of the expression of multiple genes involved in insulin sensitivity and lipogenesis in the EAT.

Cinnamon extract attenuates TNF-alpha-induced intestinal lipoprotein ApoB48 overproduction by regulating inflammatory, insulin, and lipoprotein pathways in enterocytes.

We have previously reported that the obesity-associated proinflammatory cytokine, TNF-alpha, stimulates the overproduction of intestinal apolipoprotein (apo) B48 containing lipoproteins. In the current study, we have evaluated whether a water-soluble cinnamon extract [CE (Cinnulin PF)] attenuates the dyslipidemia induced by TNF-alpha in Triton WR-1339 treated hamsters, and whether CE inhibits the oversecrection of apoB48-induced by TNF-alpha in enterocytes in a 35S labeling study. In vivo, oral treatment of Cinnulin PF (50 mg per kg BW), inhibited the postprandial overproduction of apoB48-containing lipoproteins and serum triglyceride levels. In ex vivo 35S labeling studies, CE (10 and 20 microg/ml) inhibited the oversecretion of apoB48 induced by TNF-alpha treated enterocytes into the media. To determine the molecular mechanisms, TNF-alpha treated primary enterocytes isolated from chow-fed hamsters, were incubated with CE (10 microg/ml), and the expression of the inflammatory factor genes, IL1-beta, IL-6, and TNF-alpha, insulin signaling pathway genes, insulin receptor (IR), IRS1, IRS2, phosphatidylinositol 3-kinase (PI3-K), Akt1 and phosphatase and tensin homology (PTEN), as well as the key regulators of lipid metabolism, cluster of differentiation (CD)36, microsomal triglyceride transfer protein (MTTP), and sterol regulatory element binding protein (SREBP)-1c were evaluated. Quantitative real-time PCR assays showed that CE treatment decreased the mRNA expression of IL-1beta, IL-6 and TNF-alpha, improved the mRNA expression of IR, IRS1, IRS2, PI3K and Akt1, inhibited CD36, MTTP, and PTEN, and enhanced the impaired SREBP-1c expression in TNF-alpha treated enterocytes. These data suggest that a water extract of cinnamon reverses TNF-alpha-induced overproduction of intestinal apoB48 by regulating gene expression involving inflammatory, insulin, and lipoprotein signaling pathways. In conclusion, Cinulin PF improves inflammation related intestinal dyslipidemia.

Biological activity assessment of a novel contraceptive antimicrobial agent.

Microbicides are a new category of compounds being developed as a prophylactic approach for the prevention of transmission of sexually transmitted diseases (STDs), including the human immunodeficiency virus (HIV). These are primarily being developed as women-controlled methods, with the target of designing new compounds or formulations that can be used without the knowledge of a male partner. Microbicide screening can be initially based on their hyaluronidase-inhibiting (HI) activity, as this enzyme plays a major role in the sperm and microbe penetration into the substrate. Derivatives of hesperidin, a citrus flavonoid glycoside, have been reported in the literature for their HI effects. Hesperidin was thereby sulphonated under strictly controlled conditions and the active fraction isolated and characterized, based on its HI activity. This derivative was screened for antimicrobial and enzyme-inhibitory activities, specifically for the reproductive tract. Sulphonated hesperidin (SH) was found to completely inhibit the sperm enzymes hyaluronidase, giving an indication toward its contraceptive effects. It was also been found to inhibit various sexually transmitted pathogens, including Chlamydia trachomatis, Neisseria gonorrhoea, HIV, and Herpes Simplex virus type 2 (HSV-2). Its safety assessment was based on its noninterference in sperm motility and its penetration through the cervical mucus, and no effect on the growth of lactobacilli, the normal vaginal flora. It was also found to be nontoxic to the HIV substrate cells (MT2 cells). The study concludes that sulphonated hesperidin can be developed as a potential microbicide for a dual prophylaxis of contraception and transmission of STDs and AIDS.

Alterations of antioxidant trace elements (Zn, Se, Cu) and related metallo-enzymes in plasma and tissues following burn injury in rats.

To improve the nutritional support for burn patients, we evaluated the alterations of selenium, zinc and copper (Se, Zn and Cu) and their possible contributions to an unbalanced antioxidant response to burn injury. These trace elements and the related antioxidant enzymes, glutathione peroxidase (GPx) and superoxide dismutase (SOD), were studied both in plasma (or serum) and tissues of 20% total body surface area (TBSA) burned rats for 10 days. While plasma Se and serum Zn levels significantly decreased 6 h after burn injury, serum Cu levels increased after 1 day and remained elevated the following 9 days. Selenium levels increased in kidney but decreased progressively in liver. The hepatic Zn and Cu concentrations followed a biphasic increase following burn injury. During the first day, GPx activity decreased in plasma and remained unchanged in the organs, except for a moderate diminution in the liver. Liver Cu/Zn SOD activity increased from 6 h to 4 days. In summary, following burn injury, copper and zinc were redistributed to the liver and selenium to the kidney with non-detectable changes in the muscle and brain. Changes in antioxidant enzyme activities following burn injury were significant mainly in the plasma. Early combined antioxidant supplementation to maintain and restore antioxidant status in burn patients requires further study.

Developmental changes in expression of myeloid cell leukemia-1 in human germ cells during oogenesis and early folliculogenesis.

The regulation of germ cell number in the developing ovary is central to female reproduction. Members of the Bcl-2 family of proapoptotic and antiapoptotic proteins have been implicated in this process in rodents. We investigated the expression of Mcl-1, Bcl-2, Bax, and BAD at 13-21 gestational wk in the human fetal ovary and of Mcl-1 in the adult ovary. mRNA expression of Mcl-1 and its short form Mcl-1s, Bcl-2, Bax, and BAD was demonstrated in fetal ovary by RT-PCR. Hybridization array analysis suggested a selective increase in Mcl-1 expression between 14 and 18 wk gestation, which was confirmed by quantitative PCR. There was a corresponding change in the expression of Mcl-1 protein, detected by immunohistochemistry, from germ cells at the periphery of the ovary at 14-16 wk to the largest germ cells, including oocytes within newly formed primordial follicles, at 21 wk. Mcl-1 was also expressed by oocytes of primordial and preantral follicles in the adult. Bax and BAD immunostaining was detected in both somatic and germ cells in the fetal ovary, whereas Bcl-2 was restricted to somatic cells: no changes in expression were observed. Apoptotic cells, detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, were observed in all fetal ovaries but were infrequent. These results confirm that Bcl-2 family members are differentially expressed in several cell types within the developing human ovary. Increased mRNA expression and the changing distribution of Mcl-1 in germ cells as they develop into primordial follicles as well as persistence in the growing oocyte in the adult may indicate an important role for this survival/antiapoptotic factor throughout germ cell development and maturation.

Effects of a high polyunsaturated fat diet and vitamin E supplementation on high-density lipoprotein oxidation in humans.

Oxidative modification of high-density lipoproteins (HDL) impairs several biologic functions critical to its role in reverse cholesterol transport. We therefore investigated the effect of dietary polyunsaturated fat and vitamin E on the kinetics of HDL oxidation. Ten subjects were fed sequentially: a baseline diet in which the major fat source was olive oil; a high polyunsaturated fat diet in which the major fat source was safflower oil; and the safflower oil diet plus 800 I.U. vitamin E per day. Plasma lipoprotein levels, vitamin E content, fatty acid composition, and oxidation lag time and rate were determined after 3 weeks on each diet. The polyunsaturated fat diet increased the mean HDL(2) lag time from 45.8+/-12.5 to 83.3+/-11.6 min with no change in oxidation rate. Addition of vitamin E further increased the HDL(2) lag time to 115.6+/-4.4 min and decreased the HDL(2) oxidation rate 10-fold. Neither the polyunsaturated diet alone nor the diet with vitamin E supplementation had any effect on HDL(3) oxidation. We conclude that under conditions of controlled dietary fat intake, a high polyunsaturated fat intake does not increase the oxidation susceptibility of HDL subfractions, and that in this setting, vitamin E supplementation reduces the oxidation susceptibility of HDL(2). These data suggest that antioxidants could influence HDL function in vivo.

Potential antioxidant effects of zinc and chromium supplementation in people with type 2 diabetes mellitus.

OBJECTIVE: To determine the effects of combined zinc (Zn) and chromium (Cr) supplementation on oxidative stress and glucose homeostasis of people with type 2 diabetes. DESIGN: Tunisian adult subjects with HbA1C > 7.5% were supplemented for 6 months with 30 mg/d of Zn as Zn gluconate or 400 microg/d of Cr as Cr pidolate or combined Zn/Cr supplementation or placebo. The effects of supplementation on plasma zinc (Zn), copper (Cu), selenium (Se), urinary Zn, Cr, plasma thiobarbituric acid reactive substances (TBARS), Cu-Zn superoxide dismutase (SOD) and Se glutathione peroxidase (GPx) in red blood cells, blood lipids and lipoproteins, HbA1C and fasting glucose were measured at the beginning of the study and after six months. RESULTS: At the beginning of the study, more than 30% of the subjects may have been Zn deficient with plasma Zn values less than 10.7 mircomol/L, whereas levels of plasma Cu, Se and antioxidant RBC enzyme activities were in the normal ranges. Following supplementation, there were significant decreases of plasma TBARS in the Cr (13.6%), Zn (13.6%) and Zn/Cr (18.2%) groups with no significant changes in the placebo group. The value for the TBARS of the control healthy Tunisian subjects was 2.08 +/- 0.04 micromol/L and that of the Tunisian subjects with diabetes was 3.32 +/- 0.05 micromol/L. This difference of 1.24 micromol/L between the control group and the subjects with diabetes was reduced from 36% to 50% in the three supplemented groups. Supplementation did not modify significantly HbAIC nor glucose homeostasis. No adverse effects of Zn supplementation were observed on Cu status. HDL cholesterol nor interactions in Zn or Cr. CONCLUSIONS: These data suggest the potential beneficial antioxidant effects of the individual and combined supplementation of Zn and Cr in people with type 2 DM. These results are particularly important in light of the deleterious consequences of oxidative stress in people with diabetes.

Pro-oxidant effect of vitamin E in cigarette smokers consuming a high polyunsaturated fat diet.

Dietary polyunsaturated fats and vitamin E are associated with reduced risk for atherosclerosis, but in smokers, they could promote lipid oxidation. Therefore, we examined the effects of a high polyunsaturated fat diet and vitamin E supplementation on measures of lipid oxidation in cigarette smokers. Ten subjects who smoked >1 pack of cigarettes per day were sequentially fed the following: a baseline diet in which the major fat source was olive oil, a diet in which the major fat source was high-linoleic safflower oil, and finally, the safflower oil diet plus 800 IU vitamin E per day. LDL oxidation lag time and rate and plasma total F(2)-isoprostanes and prostaglandin F(2alpha) (PGF(2alpha)) were determined after 3 weeks on each diet. The safflower oil diet increased total F(2)-isoprostanes from 53.0+/-7.2 to 116.2+/-11.2 nmol/L and PGF(2alpha) from 3.5+/-0.2 to 5.5+/-0.5 nmol/L, without changing LDL oxidation parameters. Addition of vitamin E prolonged mean LDL oxidation lag time but, paradoxically, further increased F(2)-isoprostanes to 188.2+/-10.9 nmol/L and PGF(2alpha) to 7.8+/-0.4 nmol/L. These data suggest that vitamin E may function as a pro-oxidant in cigarette smokers consuming a high polyunsaturated fat diet.

EDTA chelation effects on urinary losses of cadmium, calcium, chromium, cobalt, copper, lead, magnesium, and zinc.

The efficacy of a chelating agent in binding a given metal in a biological system depends on the binding constants of the chelator for the particular metals in the system, the concentration of the metals, and the presence and concentrations of other ligands competing for the metals in question. In this study, we make a comparison of the in vitro binding constants for the chelator, ethylenediaminetetraacetic acid, with the quantitative urinary excretion of the metals measured before and after EDTA infusion in 16 patients. There were significant increases in lead, zinc, cadmium, and calcium, and these increases roughly corresponded to the expected relative increases predicted by the EDTA-metal-binding constants as measured in vitro. There were no significant increases in urinary cobalt, chromium, or copper as a result of EDTA infusion. The actual increase in cobalt could be entirely attributed to the cobalt content of the cyanocobalamin that was added to the infusion. Although copper did increase in the post-EDTA specimens, the increase was not statistically significant. In the case of magnesium, there was a net retention of approximately 85% following chelation. These data demonstrate that EDTA chelation therapy results in significantly increased urinary losses of lead, zinc, cadmium, and calcium following EDTA chelation therapy. There were no significant changes in cobalt, chromium, or copper and a retention of magnesium. These effects are likely to have significant effects on nutrient concentrations and interactions and partially explain the clinical improvements seen in patients undergoing EDTA chelation therapy.

Insulin-like biological activity of culinary and medicinal plant aqueous extracts in vitro.

To evaluate the possible effects on insulin function, 49 herb, spice, and medicinal plant extracts were tested in the insulin-dependent utilization of glucose using a rat epididymal adipocyte assay. Cinnamon was the most bioactive product followed by witch hazel, green and black teas, allspice, bay leaves, nutmeg, cloves, mushrooms, and brewer's yeast. The glucose oxidation enhancing bioactivity was lost from cinnamon, tea, witch hazel, cloves, bay leaf and allspice by poly(vinylpyrrolidone) (PVP) treatment, indicating that the active phytochemicals are likely to be phenolic in nature. The activity of sage, mushrooms, and brewers's yeast was not removed by PVP. Some products such as Korean ginseng, flaxseed meal, and basil have been reported to be effective antidiabetic agents; however, they were only marginally active in our assay. Our technique measures direct stimulation of cellular glucose metabolism, so it may be that the active phytochemicals in these plants improve glucose metabolism via other mechanisms or that this in vitro screening is not a reliable predictor of hypoglycemic effects in vivo for some products. In summary, the positive effects of specific plant extracts on insulin activity suggest a possible role of these plants in improving glucose and insulin metabolism.

Chromium in the prevention and control of diabetes.

Chromium is an essential nutrient involved in the metabolism of glucose, insulin and blood lipids. Suboptimal dietary intake of chromium is associated with increased risk factors associated with diabetes and cardiovascular diseases. Within the past five years, chromium has been shown to improve glucose and related variables in subjects with glucose intolerance and type 1, type 2, gestational and steroid-induced diabetes. Severe neuropathy and glucose intolerance of a patient on total parenteral nutrition, who was receiving currently recommended levels of chromium, were reversed by additional supplemental chromium. Chromium increases insulin binding to cells, insulin receptor number and activates insulin receptor kinase leading to increased insulin sensitivity. Additional studies are urgently needed to elucidate the mechanism of action of chromium and its role in the prevention and control of diabetes.

EDTA chelation therapy does not selectively increase chromium losses.

Chelation therapy and supplemental Cr have both been shown to lead to improved blood glucose, lipids, and insulin activity. Chelation therapy leads to the removal of toxic as well as essential metals. To determine if chelation therapy leads to increased urinary Cr losses and altered Cr homeostasis, 2 groups of subjects (1 group that had undergone only 1 or no chelation therapy and 1 group in which all subjects had undergone at least 19 chelation sessions) were evaluated for differences in possible Cr homeostasis based on urinary Cr losses. There were no significant differences in urinary Cr losses between the two groups of subjects and there were no significant increases in urinary Cr losses resulting from chelation therapy. Increases in urinary Cr losses were strongly influenced by supplementation but not chelation therapy.

The insulin-like growth factor system in the GT1-7 GnRH neuronal cell line.

Evidence suggests that insulin-like growth factors (IGFs; IGF-I and IGF-II) are involved in the regulation of reproductive function including the development of the gonadotropin-releasing hormone (GnRH) neuronal system and the modulation of GnRH secretory activities. To further characterize the regulatory role of the IGF system on GnRH neuronal function, we have examined the gene expression of IGF-I, IGF-II, IGF-I receptor (IGF-IR), and IGF-binding proteins (IGFBPs) in a GnRH neuronal cell line (GT1-7 cells). The relative effects of IGFs and insulin on GnRH secretion by these cells was also investigated. RT-PCR analysis demonstrated IGF-I, IGF-II and IGF-IR mRNAs in GT1-7 cells. The mRNAs for IGFBP-2, -3, -4, -5 and -6 but not IGFBP-1 were also detected. Immunoreactive protein bands for IGFBP-2, -4 and -5 but not for other IGFBPs were demonstrated by Western blot with IGFBP-5 appearing to be the most abundant IGFBP secreted by GT1-7 cells. IGFBP-5 production by GT1-7 cells was stimulated by both IGF-I and IGF-II in a dose-dependent manner with approximately equal potency, whereas insulin caused no significant effect. GnRH secretion by GT1-7 cells treated with IGF-I or IGF-II but not insulin showed an increase (80-100%) at 2 h of treatment followed by a decrease (46%) at 6 h that continued up to 24 h. We conclude that the expression of IGFs, IGF-IR and IGFBPs and their interactions in the regulation of GnRH secretion by GT1-7 cells as demonstrated by our study provide a basis for an autocrine regulatory role for the IGF system in GnRH neuronal secretory activities.

Overproduction of insulin in the chromium-deficient rat.

The hypothesis that the insulin secretory hyperresponsiveness observed in rats with diet-induced insulin resistance may be a basic characteristic of dietary chromium (Cr) deficiency was evaluated. Two groups of weanling rats were fed ad libitum a purified diet containing 64% sucrose, 20% casein, 5% corn oil, and the recommended levels of vitamins and minerals without added Cr. Cr-deficient (-Cr) rats were provided with distilled drinking water only, while Cr-supplemented (+Cr) rats received water containing 5 ppm Cr as CrCl3. A third group of rats fed a commercial chow diet served as sucrose controls. Effects of Cr deficiency were assessed by comparing fasting levels of glucose, insulin, and plasma lipids in blood samples collected biweekly from the -Cr and +Cr groups over a 3-month period. Both groups of rats fed the low-Cr sucrose diet developed a transient hyperinsulinemia and hyperlipidemia relative to the chow-fed control rats. There were significant effects of Cr supplementation on plasma triglycerides during the initial 2 weeks of dietary adaptation. Effects of the low-Cr diet were evaluated after the 12-week period by comparing the insulin response area and glucose clearance during a 40-minute intravenous glucose tolerance test (IVGTT). The rates of glucose clearance (KG) in -Cr and +Cr rats were similar (4.2 +/- 1.0 and 4.3 +/- 0.8%/min, respectively) and were comparable to the K(G) in chow-fed rats (4.6 +/- 0.8). In contrast, insulin secretory responses in -Cr rats were exaggerated (area, 14,083 +/- 3,399 microU/mL x min), being twofold greater (P < .05) relative to the +Cr group (6,183 +/- 864). The insulin secretory response area in chow-fed rats (7,081 +/- 408 microU/mL x min) was similar to the value in the +Cr group. These observations provide support for the hypothesis that Cr deficiency can lead to elevated insulin secretory responses to glucose.

Reversal of corticosteroid-induced diabetes mellitus with supplemental chromium.

AIMS: To determine if the stress of corticosteroid treatment increases chromium (Cr) losses and if corticosteroid-induced diabetes (steroid diabetes) can be reversed by supplemental chromium. METHODS: The effects of corticosteroid treatment on chromium losses of 13 patients 2 days prior to steroid administration and the first 3 days following treatment were determined. Since steroid-induced diabetes was associated with increased chromium losses and insufficient dietary chromium is associated with glucose intolerance and diabetes, we treated three patients with steroid-induced diabetes with 600 microg per day of chromium as chromium picolinate. RESULTS: Urinary chromium losses following corticosteroid treatment increased from 155+/-28 ng/d before corticosteroid treatment to 244+/-33 ng/d in the first 3 days following treatment. Chromium supplementation of patients with steroid-induced diabetes resulted in decreases in fasting blood glucose values from greater than 13.9 mmol/l (250 mg/dl) to less than 8.3 mmol/l (150 mg/dl). Hypoglycaemic drugs were also reduced 50% in all patients when given supplemental chromium. CONCLUSIONS: These data demonstrate that corticosteroid treatment increases chromium losses and that steroid-induced diabetes can be reversed by chromium supplementation. Follow-up, double-blind studies are needed to confirm these observations.

Effects of resistance training and chromium picolinate on body composition and skeletal muscle in older men.

The effects of chromium picolinate (CrPic) supplementation and resistance training (RT) on skeletal muscle size, strength, and power and whole body composition were examined in 18 men (age range 56-69 yr). The men were randomly assigned (double-blind) to groups (n = 9) that consumed either 17.8 micromol Cr/day (924 microg Cr/day) as CrPic or a low-Cr placebo for 12 wk while participating twice weekly in a high-intensity RT program. CrPic increased urinary Cr excretion approximately 50-fold (P < 0.001). RT-induced increases in muscle strength (P < 0.001) were not enhanced by CrPic. Arm-pull muscle power increased with RT at 20% (P = 0.016) but not at 40, 60, or 80% of the one repetition maximum, independent of CrPic. Knee-extension muscle power increased with RT at 20, 40, and 60% (P < 0.001) but not at 80% of one repetition maximum, and the placebo group gained more muscle power than did the CrPic group (RT by supplemental interaction, P < 0.05). Fat-free mass (P < 0.001), whole body muscle mass (P < 0.001), and vastus lateralis type II fiber area (P < 0.05) increased with RT in these body-weight-stable men, independent of CrPic. In conclusion, high-dose CrPic supplementation did not enhance muscle size, strength, or power development or lean body mass accretion in older men during a RT program, which had significant, independent effects on these measurements.

Chromium, glucose intolerance and diabetes.

Within the last 5 years chromium (Cr) has been shown to play a role in glucose intolerance, Type 2 diabetes mellitus (Type 2 DM), and gestational diabetes. In addition, diabetes and the neuropathy of a patient on home parenteral nutrition were alleviated when supplemental Cr was added to total parenteral nutrition (TPN) solutions. In a study conducted in China that has been supported by studies in the United States, supplemental Cr as Cr picolinate improved the blood glucose, insulin, cholesterol, and hemoglobin A1C in people with Type 2 DM in a dose dependent manner. Follow-up studies of > 1 year have confirmed these studies. The requirement for Cr is related to the degree of glucose intolerance: 200 microg/day of supplemental Cr is adequate to improve glucose variables of those who are mildly glucose intolerant. However, people with more overt impairments in glucose tolerance and diabetes usually require more than 200 microg/day. Daily intake of 8 microg of Cr per kg body weight was also more effective than 4 microg/kg in women with gestational diabetes. The mechanism of action of Cr involves increased insulin binding, increased insulin receptor number, and increased insulin receptor phosphorylation. In summary, supplemental Cr has been shown to have beneficial effects without any documented side effects on people with varying degrees of glucose intolerance ranging from mild glucose intolerance to overt Type 2 DM.

Regulation of PTP-1 and insulin receptor kinase by fractions from cinnamon: implications for cinnamon regulation of insulin signalling.

Bioactive compound(s) extracted from cinnamon potentiate insulin activity, as measured by glucose oxidation in the rat epididymal fat cell assay. Wortmannin, a potent PI 3'-kinase inhibitor, decreases the biological response to insulin and bioactive compound(s) from cinnamon similarly, indicating that cinnamon is affecting an element(s) upstream of PI 3'-kinase. Enzyme studies done in vitro show that the bioactive compound(s) can stimulate autophosphorylation of a truncated form of the insulin receptor and can inhibit PTP-1, a rat homolog of a tyrosine phosphatase (PTP-1B) that inactivates the insulin receptor. No inhibition was found with alkaline phosphate or calcineurin suggesting that the active material is not a general phosphatase inhibitor. It is suggested, then, that a cinnamon compound(s), like insulin, affects protein phosphorylation-dephosphorylation reactions in the intact adipocyte. Bioactive cinnamon compounds may find further use in studies of insulin resistance in adult-onset diabetes.