Improved Insulin Levels Research Articles

Pre-germinated brown rice prevents high-fat diet induced hyperglycemia through elevated insulin secretion and glucose metabolism pathway in C57BL/6J strain mice.

This study investigated the effect and mechanism of pre-germinated brown rice (PGBR) prevented hyperglycemia in C57BL/6J mice fed high-fat-diet (HFD). Normal six-week-old mice were randomly divided into three groups. Group 1 was fed standard-regular-diet (SRD) and group 2 was fed HFD for 16 weeks. In group 3, the mice were fed a HFD with its carbohydrate replaced with PGBR for 16 weeks. Comparing the SRD and HFD groups, we found the HFD group had higher blood pressure, higher concentrations of blood glucose and HbA1c. The HFD group had less protein expression of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), phosphatidylinositol-3-kinase (PI3K), glucose transporter-4 (GLUT-4) and glucokinase (GCK) and greater expression of glucogen synthase kinase (GSK) in skeletal muscle. The HFD group also had less expression of IR, serine/threonine kinase PI3K-linked protein kinase B (Akt/PKB), AMP-activated protein kinase (AMPK), GCK and peroxisome proliferator-activated receptor γ (PPARγ) in liver. In the HFD + PGBR group, the PGBR could reverse the disorders of blood pressure, blood glucose, HbA1c and increase insulin concentration. PGBR increased the IR, IRS-1, PI3K, Akt, GLUT-1 and GLUT-4 proteins, and ameliorated AMPK, GCK, GSK and PPARγ proteins. Together, PGBR prevented HFD-induced hyperglycemia through improving insulin levels, insulin receptor, glucose transporters and enhancing glucose metabolism.

Metabolic and Inflammatory Signaling are Influenced by Consumption of Polyphenol‐rich Whole‐Fruit Extracts and Purified Phytochemicals in High‐fat Fed Mice (LB419)

A number of reports show that many different phytochemicals favorably influence metabolism and reduce inflammatory markers. Our trial tested the relative potency of purified compounds or whole foods in parallel, using the high‐fat fed C57BL/6J mouse model. The model tested and ranked effects of fruit extracts derived from apple peel, whole sweet cherries and grapes, along with purified compounds including quercetin, resveratrol, and ellagic acid in an attempt to design more‐potent combinations. Polyphenol‐rich fruit extracts and purified compounds were mixed into a high‐fat (60% of total kcal) obesigenic rodent diet and fed to mice along with low‐fat and high‐fat control diets for 10 weeks. Serum circulating factors were measured using a magnetic bead multiplex assay (Milliplex, Millipore Corp.). Mice fed the high‐fat control diet became obese and lost normal glucose control. Serum insulin levels were >1500 pg/mL in the high‐fat controls versus 90% of the high‐fat level (P< 0.01). Quercetin and extracts from grape, cherry, and apple peel also showed improved insulin levels. C‐reactive protein (CRP) concentrations were higher in all high‐fat diet groups except the mice fed a high‐fat diet containing a grape powder product. Our results point to future research in which we plan to compare the relative impact of mixtures of different commonly‐available whole foods on chronic inflammation.Grant Funding Source: Blue Mountain Horticultural Society

HYPOGLYCEMIC, HEPATO-RENAL AND ANTIOXIDANT POTENTIAL EFFECTS OF <i>CHAMOMILE</i> RECUTITA FLOWERS ETHANOLIC EXTRACT IN STREPTOZOTOCIN-DIABETIC RATS

This study was undertaken to evaluate the hypoglycemic and hepatorenal protective effect of ethanolic extract of Chamomile recutita flowers in streptozotocin-Diabetic Rats. Before the beginning of the experiments, acute and subacute studies were carried out in control animals first to investigate the LD50 of this extract. In the experimental design, adult male albino rats were divided into five groups: (1) normal control, (2) control + extract, (3) diabetic control, (4) diabetic+extract and (5) diabetic+glibenclamide (200 µg kg-1). The extract was given to the desired groups at a final dose of 500 mg kg-1 and all treatments were administered orally for 4 weeks on daily basis. Serum glucose, insulin, activities of serum marker enzymes of liver function as well as markers of kidney function was measured. The oxidative stress was assessed by measuring lipid peroxidation (TBARS) and enzyme activities of Glutathione Peroxidase (GPx) superoxide dismutase in both liver and kidney homogenates. The data showed that ethanolic flower extract of Chamomile recutita demonstrated high safety margin since the animals tolerated up to 10000 mg kg-1 body weight of the extract orally in the acute toxicity study and tolerated repeated doses up to 500 mg kg-1 for 28 days. Administration of the extract to control and diabetic rats caused significant decrease in glucose level in serum without improving insulin levels and resulted in significant increases in SOD and GPx activities with a parallel decrease in lipid peroxidation (TBARS levels) in the livers and kidneys. Furthermore, in diabetic rats, treatment with the extract resulted in significant decreases in the serum activities of liver enzymes including AST, ALT and ALP and in the levels of urea and creatinine. The hepatoprotective effect of the extract were confirmed by histological improvements in hepatic and renal tissue of the diabetic treated rats. However, the effect of the extract in diabetic rats was comparable to glibenclamide. This study demonstrates that Chamomile recutita flowers ethanolic extract has potent hypoglycemic, antioxidant and hepatorenal protective effects in diabetic rats.

Effect of Aging and Exercise Training on Plasma Insulin Concentration

Abstract Background and Aims. Previous studies have shown that aging is an important risk factor for insulin resistance and type 2 diabetes. The beneficial effects of exercise on glucose metabolism are well known. Our goal was to examine whether physical activity improves insulin levels in older individuals. Material and Methods. Plasma glucose and insulin were measured in fasting state and 2 h after a 75-g oral glucose tolerance test in young lean, sedentary, non-diabetic subjects (n=34, age 25±2 years, body mass index- BMI 24.4±0.7 kg/m2) and older, lean, sedentary, non-diabetic subjects (n=36, age 75±3 years, BMI 24.8±0.4 kg/m2), before and after 8 weeks of aerobic exercise. Training consisted of exercise (such as cycling or fast walking) 5 days/week for approximately 30 min/day. Results. Fasting plasma insulin and 2-h serum insulin levels at baseline were significantly higher in older than young subjects (11.6 μU/ml vs 10.0 μU/ml, p=0.0001, 46.3 μU/ml vs 34.0 μU/ml, p=0.0001). Fasting and 2h plasma insulin levels were reduced after 8 weeks of aerobic exercise in older subjects, with no change in body weight. Conclusion. In our study the hyperinsulinemia associated with aging can be blunted significantly by aerobic exercise in older individuals independent of any changes in body composition

Potential nephrotoxic effects produced by steroidal saponins from hydro alcoholic extract of Tribulus terrestris in STZ-induced diabetic rats

Chronic hyperglycemia leads to the development of microvascular complications like diabetic nephropathy. The present study investigated the potential effects of the hydroalcoholic extract of Tribulus terrestris, a plant of Zygophyllaceae family, on the renal complications in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by administering STZ (90 mg/kg) to the 2-days old neonates. After 6 weeks of induction, diabetic rats were treated with 50 mg/kg hydroalcoholic extract of T. terrestris for 8 weeks. The anti-hyperglycaemic nature was confirmed by reduction in blood glucose and improvement in insulin levels. Diabetic renal injury associated with decrease in total proteins and albumin levels was observed to be improved by T. terrestris extract. Glomerular filtration rate along with inflammatory and growth factors, adiponectin and erythropoietin were also improved by the treatment, though the findings were not significant. However, the beneficial antidiabetic effects of T. terrestris extract in plasma were not observed in kidney histopathology. This was confirmed by the quantitative estimation of unhydrolyzed fraction of saponins (major component: protodioscin) in plasma and kidney samples of normal and diabetic rats. Hence, it can be concluded that 8 weeks treatment with T. terrestris extract produces potential toxic effects in kidney, which are independent of its anti-diabetic action.

Omeprazole improves the anti‐obesity and antidiabetic effects of exendin‐4 in db/db mice (奥美拉唑改善唾液素‐4 对db/db小鼠的减肥与降糖作用)*

AbstractBackground: In addition to its glucoregulatory actions, exendin‐4, a stable glucagon‐like peptide‐1 receptor agonist, exhibits protective effects in the pancreas and anti‐obesity effects. Suitable combination treatment with other anti‐obesity or pancreas protective agents would be an effective approach to optimize these additional effects. In the present study, we investigated the effects of the addition of omeprazole, a proton pump inhibitor, to exendin‐4 in db/db mice, an experimental model of obesity and type 2 diabetes.Methods: The effects repeated dose treatment for 14 days with exendin‐4 (8 μg/kg, s.c.) and omeprazole (30 mg/kg, s.c.) on glycemic control, food intake, and body weight were determined in obese and hyperglycemic db/db mice. The effects of these treatments on plasma gastrin, ghrelin, and leptin levels were determined, along with effects on nausea‐like symptoms. The pancreatic effects of the repeated dose treatment were assessed by measuring %HbA1c in the circulation as well as pancreatic insulin and glucagon content and glucokinase activity.Results: Combination treatment resulted in significant decreases in plasma leptin and ghrelin levels after repeated dosing. Omeprazole improved the anorectic and body weight‐lowering effects and reversed the inhibitory effect of exendin‐4 on gastrin levels after repeated dose treatment. The 14‐day combination treatment significantly reduced glucose excursion and improved insulin levels, with a concomitant decrease in %HbA1c levels. It also improved glucokinase activity and pancreatic insulin content, with a significant decrease in glucagon content.Conclusions: Combined treatment with omeprazole with exendin‐4 reduces food intake and body weight gain, most likely through changes in plasma ghrelin and leptin levels, and improves pancreatic insulin and glucagon content by improving glucokinase activity.

Metabolic and immunomodulatory effects of n-3 fatty acids are different in mesenteric and epididymal adipose tissue of diet-induced obese mice

In studies emphasizing antiobesogenic and anti-inflammatory effects of long-chain n-3 polyunsaturated fatty acids (LC-n-3 PUFA), diets with very high fat content, not well-defined fat quality, and extreme n-6/n-3 PUFA ratios have been applied frequently. Additionally, comparative analyses of visceral adipose tissues (VAT) were neglected. Considering the link of visceral obesity to insulin resistance or inflammatory bowel diseases, we hypothesized that VAT, especially mesenteric adipose tissue (MAT), may exhibit differential responsiveness to diets through modulation of metabolic and inflammatory processes. Here, we aimed to assess dietary LC-n-3 PUFA effects on MAT and epididymal adipose tissue (EAT) and on MAT-adjacent liver and intestine in diet-induced obese mice fed defined soybean/palm oil-based diets. High-fat (HF) and LC-n-3 PUFA-enriched high-fat diet (HF/n-3) contained moderately high fat with unbalanced and balanced n-6/n-3 PUFA ratios, respectively. Body composition/organ analyses, glucose tolerance test, measurements of insulin, lipids, mRNA and protein expression, and immunohistochemistry were applied. Compared with HF, HF/n-3 mice showed reduced fat mass, smaller adipocytes in MAT than EAT, improved insulin level, and lower hepatic triacylglycerol and plasma NEFA levels, consistent with liver and brown fat gene expression. Gene expression arrays pointed to immune cell activation in MAT and alleviation of intestinal endothelial cell activation. Validations demonstrated simultaneously upregulated pro- (TNFα, MCP-1) and anti-inflammatory (IL-10) cytokines and M1/M2-macrophage markers in VAT and reduced CD4/CD8α expression in MAT and spleen. Our data revealed differential responsiveness to diets for VAT through preferentially metabolic alterations in MAT and inflammatory processes in EAT. LC-n-3 PUFA effects were pro- and anti-inflammatory and disclose T cell-immunosuppressive potential.

Insulin Sensitivity After Maximal and Endurance Resistance Training

The purpose of the study was to compare the effects of maximal resistance training (MRT) vs. endurance resistance training (ERT) on improvements in insulin levels and glucose tolerance in overweight individuals at risk of developing type 2 diabetes. Eighteen participants with baseline values suggesting impaired glucose tolerance were randomly assigned to 1 of 2 groups. Group 1 engaged in supervised MRT (Bernstein inverted pyramid system: 5 × 3-4, 60-85% 1 repetition maximum [1RM]), 3 d·wk(-1) over 4 months, whereas members of group 2 acted as controls. Later, group 2 engaged in supervised ERT (3 × 12-15, 45-65% 1RM), 3 d·wk(-1) over a 4 month period with the 2 prebaselines as controls. Both interventions consisted of 8 exercises that included the entire body. Glucose (fasting and 2-hour test), insulin and C-peptide measures were assessed from pre to post in both groups. The MRT led to reduced blood levels of 2-hour glucose (p = 0.044) and fasting C-peptide (p = 0.023) and decreased insulin resistance (p = 0.040). The ERT caused a significant reduction in the blood levels of insulin (p = 0.023) and concomitant positive effects on % insulin sensitivity (p = 0.054) and beta-cell function (p = 0.020). The findings indicate that both MRT and ERT lead to decreased insulin resistance in people with a risk of developing type 2 diabetes; MRT led to a greater increase in glucose uptake capacity (in muscles), whereas ERT led to greater insulin sensitivity, supporting the recommendation of both MRT and ERT as primary intervention approaches for individuals at a risk of developing type 2 diabetes.

Autonomic Dysfunction in Heart Failure and Renal Disease

EDITORIAL article Front. Physiol., 26 June 2012Sec. Integrative Physiology Volume 3 - 2012 | https://doi.org/10.3389/fphys.2012.00219

Pharmacological treatment of hyperinsulineamia in rats depends on coping style

Passive and proactive coping styles are associated with marked differences in behavioral and neuroendocrine responses. Previous studies revealed that the passive individuals are more prone to hyperinsulineamia. Likewise, we hypothesize that different coping styles may require different drugs to treat this. We tested this by treating passive and proactive rats (Roman Low Avoidance and Roman High Avoidance rats respectively) with either Rosiglitazone or with RU486. After eight days of treatment we performed and intravenous glucose tolerance test (IVGTT) and we compared the insulin and glucose levels with those measured during the IVGTT at baseline. Rosiglitazone improved insulin levels during an IVGTT in both passive and proactive coping styles. RU486, however, lowered insulin levels only in rats with a passive coping style. This study suggests that insight in the neuroendocrine differences between passive and proactive coping styles may provide an extra impulse to improve treatment of insulin resistance, since it allows the application of drugs targeted at the individual.

Culture of Impure Human Islet Fractions in the Presence of Alpha-1 Antitrypsin Prevents Insulin Cleavage and Improves Islet Recovery

Background Exocrine tissue is commonly cotransplanted with islets in autografting and allotransplantation of impure preparations. Proteases and insulin are released by acinar cells and islets, respectively, during pretransplantation culture and also systemically after transplantation. We hypothesized that released proteases could cleave insulin molecules and that addition of alpha-1 antitrypsin (A1AT) to impure islet cultures would block this cleavage, improving islet recovery and function. Methods Trypsin, chymotrypsin, and elastase (TCE) activity and insulin levels were measured in culture supernates of pure (n = 5) and impure (n = 5) islet fractions, which were isolated from deceased donors. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used to detect insulin after incubation with proteases. We assessed the effects of A1AT supplementation (0.5 mg/mL; n = 4] on TCE activity, insulin levels, culture recovery, and islet quality. The ultrastructure of islets exposed to TCE versus control medium was examined using electron microscopy (EM). Results Protease (TCE) activity in culture supernatants was indirectly proportional to the percentage purity of islets: pure, impure, or highly impure. Increasingly lower levels of insulin were detected in culture supernatants when higher protease activity levels were present. Insulin levels measured from supernatants of impure and highly impure islet preparations were 61 ± 23.7% and 34 ± 33% of that in pure preparations, respectively. Incubation with commercially available proteases (TCE) or exocrine acinar cell supernatant cleaved insulin molecules as assessed using SDS-PAGE. Addition of A1AT to impure islet preparations reduced protease activity and restored normal insulin levels as detected using enzyme-linked immunosorbent assay (ELISA) and SDS-PAGE of culture supernates. A1AT improved insulin levels to 98% ± 1.3% in impure and 78% ± 34.2% in highly impure fractions compared with pure islet fractions. A1AT supplementation improved postculture recovery of islets in impure preparations compared with nontreated controls (72% ± 9% vs 47% ± 15%). Islet viability as measured using membrane integrity assays was similar in both the control (98% ± 2%) and the A1AT-treated groups (99% ± 1%). EM results revealed a reduction or absence of secretory granules after exposure to proteases (TCE). Conclusion Culture of impure human islet fractions in the presence of A1AT prevented insulin cleavage and improved islet recovery. A1AT supplementation of islet culture media, therefore, may increase the proportion of human islet products that meet release criteria for transplantation.

Randomized clinical trial with a inulin enriched cookie on risk cardiovascular factor in obese patients

Inulin is a prebiotic with potential benefit in cardiovascular risk factors. The aim of our work is to evaluate in obese patients the effect of a inulin enriched cookie on cardiovascular risk factors. 34 patients were randomized in both branches: group I (inulin enriched cookie) Gullon SL(R) and group II (control cookie). Previous and after 1 month of the treatment, a nutritional and biochemical study was realized. 15 patients finished the procotol in each group. In group I, an increase in soluble fiber intake (inulin) was detected. In this group a significant decrease of total cholesterol (223.1 +/- 45.3 mg/dl vs 208.8 +/- 33.1 mg/dl; p < 0.05) and LDL cholesterol (142.9 +/- 39.2 mg/dl vs 131.4 +/- 28.6 mg/dl; p < 0.05) was reached. A non significant improvement in insulin levels and HOMA was detected in inulin-enriched cookie group, too. Anthropometric parameters did not change in both groups. The increase in soluble fiber intake did not produce any gastrointestinal adverse effect. The increase of fiber intake (3 g of inulin) from an enriched cookie reduced LDL cholesterol levels in obese patients.

Effects of the methanolic extracts of Zizyphus spina christi, Olea europaea and Morus alba leaves in Streptozotocin- induced diabetic rats.

Background:The present study aims to investigate the hypoglycemic, hypolipidimic and antioxidant effect of the methanolic crude extracts of Zizyphus spina christi, Morus alba and Olea europaea leaves, individually or in combination against diabetes induced rats by Streptozotocin (STZ). Results:Hyperglycemia and hyperlipidaemia except in high density lipoproteins (HDL) were observed in serum after 5 weeks of STZ administration. This was associated with a depression in hepatic glutathione (GSH) concentration as well as hepatic catalase (CAT), glutathione-s- transferase (GST) and superoxide dismutase (SOD) activates. In addition hepatic thiobarbituric acid-reactive substance (TBARS) and protein carbonyl (PC) were significantly elevated, indicating increased lipid and protein oxidation and oxidative stress. Depression in blood hemoglobin (Hb) content, serum insulin levels, total antioxidant capacity (TAOC) and nitric oxide (NO) levels as well as body weight gain were also observed in diabetic rats. Administration of 100mg/kg alcoholic extracts of Zizyphus spina christi, Morus alba and Olea europaea leaves 3 days before and after STZ injection daily for 5 weeks significantly ameliorated the oxidative stress evidenced by lowering TBARS & PC as well as increasing hepatic GSH concentration and CAT, GST and SOD activates as compared with STZ treated rats. These effects were paralleled with marked protection against STZ induced hyperglycemia and disturbance of lipid profile. They also caused a great improvement in insulin levels, TAOC, NO, Hb content and body weight gain. Conclussion:Thus, these results showed that the administration of the crude extracts of either Zizyphus spina christi, Morus alba or Olea europaea leaves individually or in combination might improve the clinical manifestation of diabetes and decrease the oxidative stress, this study supports the beneficial effects of these extracts especially Zizyphus spina christi, which showed marked amelioration and this may be attributed to the presence of saponin glycosides which have an inhibitory effect of serum glucose level in addition to enhance the cellular antioxidant defense. This activity contributes to the protection against oxidative damage in STZ induced diabetes.

Effects of the methanolic extracts of Zizyphus spina christi, Olea europaea and Morus alba leaves in Streptozotocin- induced diabetic rats.

Background:The present study aims to investigate the hypoglycemic, hypolipidimic and antioxidant effect of the methanolic crude extracts of Zizyphus spina christi, Morus alba and Olea europaea leaves, individually or in combination against diabetes induced rats by Streptozotocin (STZ). Results:Hyperglycemia and hyperlipidaemia except in high density lipoproteins (HDL) were observed in serum after 5 weeks of STZ administration. This was associated with a depression in hepatic glutathione (GSH) concentration as well as hepatic catalase (CAT), glutathione-s- transferase (GST) and superoxide dismutase (SOD) activates. In addition hepatic thiobarbituric acid-reactive substance (TBARS) and protein carbonyl (PC) were significantly elevated, indicating increased lipid and protein oxidation and oxidative stress. Depression in blood hemoglobin (Hb) content, serum insulin levels, total antioxidant capacity (TAOC) and nitric oxide (NO) levels as well as body weight gain were also observed in diabetic rats. Administration of 100mg/kg alcoholic extracts of Zizyphus spina christi, Morus alba and Olea europaea leaves 3 days before and after STZ injection daily for 5 weeks significantly ameliorated the oxidative stress evidenced by lowering TBARS & PC as well as increasing hepatic GSH concentration and CAT, GST and SOD activates as compared with STZ treated rats. These effects were paralleled with marked protection against STZ induced hyperglycemia and disturbance of lipid profile. They also caused a great improvement in insulin levels, TAOC, NO, Hb content and body weight gain. Conclussion:Thus, these results showed that the administration of the crude extracts of either Zizyphus spina christi, Morus alba or Olea europaea leaves individually or in combination might improve the clinical manifestation of diabetes and decrease the oxidative stress, this study supports the beneficial effects of these extracts especially Zizyphus spina christi, which showed marked amelioration and this may be attributed to the presence of saponin glycosides which have an inhibitory effect of serum glucose level in addition to enhance the cellular antioxidant defense. This activity contributes to the protection against oxidative damage in STZ induced diabetes.

Bioactives of Artemisia dracunculus L enhance cellular insulin signaling in primary human skeletal muscle culture

An alcoholic extract of Artemisia dracunculus L (PMI 5011) has been shown to decrease glucose and improve insulin levels in animal models, suggesting an ability to enhance insulin sensitivity. We sought to assess the cellular mechanism by which this botanical affects carbohydrate metabolism in primary human skeletal muscle culture. We measured basal and insulin-stimulated glucose uptake, glycogen accumulation, phosphoinositide 3 (PI-3) kinase activity, and Akt phosphorylation in primary skeletal muscle culture from subjects with type 2 diabetes mellitus incubated with or without various concentrations of PMI 5011. We also analyzed the abundance of insulin receptor signaling proteins, for example, IRS-1, IRS-2, and PI-3 kinase. Glucose uptake was significantly increased in the presence of increasing concentrations of PMI 5011. In addition, glycogen accumulation, observed to be decreased with increasing free fatty acid levels, was partially restored with PMI 5011. PMI 5011 treatment did not appear to significantly affect protein abundance for IRS-1, IRS-2, PI-3 kinase, Akt, insulin receptor, or Glut-4. However, PMI 5011 significantly decreased levels of a specific protein tyrosine phosphatase, that is, PTP1B. Time course studies confirmed that protein abundance of PTP1B decreases in the presence of PMI 5011. The cellular mechanism of action to explain the effects by which an alcoholic extract of A dracunculus L improves carbohydrate metabolism on a clinical level may be secondary to enhancing insulin receptor signaling and modulating levels of a specific protein tyrosine phosphatase, that is, PTP1B.

A novel mutation in the human aromatase gene: Insights on the relationship among serum estradiol, longitudinal growth and bone mineral density in an adult man under estrogen replacement treatment

ObjectiveHere we report on a new case of human aromatase deficiency in a man of 26 years of age and present the results of five year follow-up during trandermal estradiol (tE2) substitution, focusing on bone growth and mineralization. The lack of patient's compliance to tE2 treatment, resulting in low but detectable serum estradiol levels, provides helpful information about the physiological estradiol needed in serum to guarantee a complete bone maturation and mineralization. DesignClinical case report study. MethodsGenetic, biochemical and hormonal evaluations and the study of bone health were performed before and during estrogen treatment. ResultsEunuchoid body proportions, unfused epiphyses, tall stature, osteopenia, increase fasting insulin, mild astenozoospermia and a history of right cryptorchidism were present. Baseline serum FSH was slightly above the normal range and estradiol was undetectable. Genetic analysis revealed a pattern of compound heterozygosity due to 23 bp deletion in exon IV and a point mutation in the first nucleotide of intron IX of the CYP19A1 gene, respectively. The closure of epiphyseal cartilage, the normalization of bone BMD and bone turnover markers, and the improvement of insulin levels were reached during tE2 only when serum estradiol raised above 73 pmol/L. Sperm parameters and overweight did not improve with substitutive therapy. ConclusionsThis new case of aromatase deficiency underlines the role of estrogen on skeletal maturation, BMD, metabolic abnormalities and gonadal axis. It provides evidence on the need not only of a continuous estrogen replacement, but also of ensuring adequate estradiol levels in serum in order to ensure a complete bone maturation and mineralization and to prevent the worsening of body skeletal proportions. The comprehension of this physiological aspect has relevant clinical significance especially for the development of new therapeutic strategies useful to treat growth disorders by targeting serum estradiol in men.

Clinical, endocrine, and metabolic effects of acarbose, a α-glucosidase inhibitor, in overweight and nonoverweight patients with polycystic ovarian syndrome

To determine the clinical, endocrine, and metabolic effects of acarbose use in overweight and nonoverweight patients with polycystic ovarian syndrome (PCOS). Prospective analysis. Gynecology and infertility clinic of a tertiary care medical center. Seventy-four patients with PCOS and 30 healthy women. Acarbose use. Clinical findings of hyperandrogenism, body mass indices, LH, FSH, DHEAS, total T, PRL, basal insulin, fasting glucose/insulin levels, and lipid profiles. Acarbose treatment improved LH/FSH levels, decreased total T, DHEAS, basal insulin, low-density lipoprotein, very low-density lipoprotein, and triglyceride levels, and increased high-density lipoprotein levels in patients with PCOS. Basal insulin and fasting glucose/insulin levels reacted more significantly in overweight patients undergoing acarbose treatment. Acarbose has been found to improve insulin levels and thus glucose/insulin ratios more effectively in overweight patients compared with nonoverweight patients with PCOS. This drug seems to be an effective drug to be used in overweight as well as nonoverweight patients with PCOS.

A prospective, randomized clinical trial comparing chromium picolinate to metformin for the treatment of insulin resistance in obese, hispanic women with polycystic ovarian syndrome

Hispanic women with polycystic ovarian syndrome (PCOS) may have more severe insulin resistance (IR) than other ethnic groups. Obesity, a problem in this population, exacerbates IR further. Yet metformin (MET) has limited effect on IR in obese patients. Chromium picolinate (CP) has been used to improve insulin levels in diabetics. We hypothesized that CP, alone or with MET, may be more effective in lowering insulin in our Hispanic, obese PCOS-IR population. Our objective was to compare fasting insulin (INS) and other parameters (glucose, lipids, androgens, estrogens, chromium, body mass index (BMI), blood pressure) in subjects treated for 3 months with MET, CP, or CP plus metformin (CP-MET).

Metformin treatment does not affect total leptin levels and free leptin index in obese patients with polycystic ovary syndrome

Leptin, particularly in its free form, is deeply involved in the regulation of energy balance. Insulin was suggested to influence plasmatic leptin levels and soluble leptin receptor in humans. However, this study indicates that metformin treatment, although improving insulin levels, does not exert a significant effect on either total leptin level or free leptin index in obese women with hyperinsulinemia and PCOS.

Improvement of glucose-primed intravenous glucose tolerance and correction of acute insulin decrement by glipizide in type II diabetes

Improved glucose disposal after repeated intravenous (IV) glucose loads, known as the Staub effect, is absent in both type I and type II diabetes. Acute decrements of insulin secretion (AID) are observed following the early phase of insulin release on IV glucose stimulation in non-insulin-dependent diabetes mellitus (NIDDM). The AID cannot be corrected by acute infusions of glyburide or glipizide, or phentolamine, or by glycemic control after 2 weeks of intensive insulin treatments. Fifteen male subjects had 3 hourly successive IV glucose tolerance tests before and after 6 months of glipizide, at a final maintenance dose of 30 ± 3 mg/d. Before treatment, AID, defined as the difference of the lowest of post IV glucose 7- or 10-minute samples from the preceding baseline insulin levels, was detected in the three loads: −6.4 ± 1.9 μU/mL in the first, and then more consistently in the second and third loads, −11 ± 2 μU/mL, and −17 ± 9 μU/mL, respectively. There was a stepwise increase in insulin sums after each load. After glipizide therapy, the AIDs following all three IV glucose loads were no longer demonstrable; both insulin values, as well as insulin sums, were significantly elevated after all three glucose loads. While in the untreated state, the Staub effect was absent: serum glucose disappearances (K), corrected for glycosuria, were K1 = 0.52 ± 0.02, K2 = 0.50 ± 0.04, and K3 = 0.52 ± 0.03. After glipizide, fasting glucose decreased from 215 ± 12 mg/dL to 132 ± 9 mg/dL, glucose values during the triple IV tolerance tests were significantly lower, and the glycohemoglobin decreased from 9.9% ± 0.5% to 8.2% ± 0.03%. Furthermore, glucose disappearance rates were improved: K1 = 0.62 ± 0.02, K2 = 0.68 ± 0.02, and K3 = 0.77 ± 0.04, also defining a positive Staub effect. There was a positive correlation between the glucose disappearance rates and the treatment-induced improvement of early insulin release in the second and third glucose loads (the difference from baseline of the higher of either the 3-minute or the 5-minute post IV samples). There was also a positive correlation between improvement in glucose disappearance rates in the third load with the total insulin sums. Mean AID in untreated overt NIDDM is potentiated by IV glucose priming, even while insulin levels increase. After treatment with glipizide, the AID is either reverted or insignificant, and the Staub effect is restored, along with post IV glucose improvement in insulin levels. Chronic sulfonylurea administration appears at present to be the only known conventional treatment restoring post IV glucose Staub effect and ameliorating the AID of NIDDM.