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Insulin
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1. TC10alpha is required for insulin-stimulated glucose uptake in adipocytes.
Match Strength: 6.328

Previous studies have suggested that activation of the Rho family member GTPase TC10 is necessary but not sufficient for the stimulation of glucose transport by insulin. We show here that endogenous TC10alpha is rapidly activated in response to insulin in 3T3L1 adipocytes in a phosphatidylinositol 3-kinase-independent manner, whereas platelet-derived growth factor was without effect. Knockdown of TC10alpha but not TC10beta by RNA interference inhibited insulin-stimulated glucose uptake as well as the translocation of the insulin-sensitive glucose transporter GLUT4 from intracellular sites to ... Read More »
» Published in Endocrinology. 2007 Jan;148(1):27-33. Epub 2006 Sep 28.

2. Insulin-induced oedema in children and adolescents.
Match Strength: 6.208

Oedema is an uncommon complication of insulin therapy, which has only rarely been reported in childhood. We describe a case of a 12-year-old girl with newly diagnosed type 1 diabetes, who presented with oedema of the lower extremities and periorbitally, one day after the initiation of insulin treatment. Other causes of oedema were excluded. Following administration of frusemide, oedema resolved within ten days. An extended review of the literature revealed only nine cases of insulin-induced oedema in children and adolescents aged ... Read More »
» Published in J Paediatr Child Health. 2006 Oct;42(10):655-7.

3. Glycemic control with continuous subcutaneous insulin infusion with use of U-500 insulin in a pregnant patient.
Match Strength: 6.003

OBJECTIVE: To demonstrate the benefits and to advocate the safety and efficacy of using an insulin pump with U-500 insulin in comparison with U-100 insulin for a pregnant patient with diabetes requiring massive doses of insulin. METHODS: We present a detailed case report about the use of continuous subcutaneous insulin infusion with U-500 insulin during pregnancy. Dose calculation is reviewed, and the benefits of insulin pump therapy in patients with diabetes are discussed. RESULTS: A 34-year-old white woman, with a history of type 2 diabetes for 7 years, was seen at 17 weeks of gestation ... Read More »
» Published in Endocr Pract. 2006 Sep-Oct;12(5):542-4.

4. How to start insulin treatment: Earlier or delayed insulin therapy.
Match Strength: 5.989

No consensus exists as to the best time for starting insulin treatment in patients with type 2 diabetes. Glucose toxicity is a significant factor which affects the approach to treatment at various stages of the disease. Those who advocate early insulin use cite studies which have used CSII or intensive insulin therapy in newly-diagnosed type 2 diabetics and have achieved long-term glycemic control without medication, similar to the "honeymoon" in type 1 diabetic patients. Although there are studies showing improved control with maximal dose sulfonylurea therapy, glucose control takes longer to ... Read More »
» Published in Diabetes Res Clin Pract. 2006 Nov 30;74 Suppl 1:S17-9. Epub 2006 Sep 25.

5. Altered glucose homeostasis in mice lacking the receptor protein tyrosine phosphatase sigma.
Match Strength: 5.986

Several protein tyrosine phosphatases (PTPs) expressed in insulin sensitive-tissues are proposed to attenuate insulin action and could act as key regulators of the insulin receptor (IR) signaling pathway. Among these PTPs, RPTPsigma is expressed in relatively high levels in insulin-target tissues. We show that RPTPsigma-/- knockout mice have reduced plasma glucose and insulin concentrations in the fasted state compared with their wild-type siblings. The knockout animals were also more sensitive to exogenous insulin as assayed by insulin-tolerance tests. Despite increased whole-body insulin ... Read More »
» Published in Can J Physiol Pharmacol. 2006 Jul;84(7):755-63.

6. Marked increase of insulin gene transcription by suppression of the Rho/Rho-kinase pathway.
Match Strength: 5.802

The hallmarks of type 2 diabetes are pancreatic beta-cell dysfunction and insulin resistance. It has been suggested that Rho/Rho-kinase is a mediator of insulin signaling, and thereby involved in the development of insulin resistance, regulation of insulin action, and glucose homeostasis, but the role of Rho/Rho-kinase in beta-cells remained unknown. The aim of this study was to examine the possible role of Rho/Rho-kinase in beta-cell function. Immunostaining showed that RhoA was expressed in mature beta-cells, with higher expression observed in beta-cells of diabetic C57BL/KsJ-db/db mice ... Read More »
» Published in Biochem Biophys Res Commun. 2006 Nov 10;350(1):68-73. Epub 2006 Sep 12.

7. Characterization of alterations in carbohydrate metabolism in children with Prader-Willi syndrome.
Match Strength: 5.743

OBJECTIVE: To study carbohydrate metabolism and insulin sensitivity and secretion in children and adolescents with Prader-Willi syndrome (PWS) compared with multifactorial obesity (MO) controls. PATIENTS AND METHODS: Seventy-five patients with PWS and 395 controls with MO were studied by oral glucose tolerance test. Insulin resistance (IR) and beta-cell function were assessed by homeostasis model assessment (HOMA), insulin glucose index, fasting insulin and insulin sensitivity index. RESULTS: The incidence of diabetes mellitus was 0% in PWS and 1.5% in MO, while carbohydrate intolerance was 9 ... Read More »
» Published in J Pediatr Endocrinol Metab. 2006 Jul;19(7):911-8.

8. Imaging docking and fusion of insulin granules induced by antidiabetes agents: sulfonylurea and glinide drugs preferentially mediate the fusion of newcomer, but not previously docked, insulin granules.
Match Strength: 5.492

Sulfonylurea and glinide drugs, commonly used for antidiabetes therapies, are known to stimulate insulin release from pancreatic beta-cells by closing ATP-sensitive K+ channels. However, the specific actions of these drugs on insulin granule motion are largely unknown. Here, we used total internal reflection fluorescence (TIRF) microscopy to analyze the docking and fusion of single insulin granules in live beta-cells exposed to either the sulfonylurea drug glibenclamide or the glinide drug mitiglinide. TIRF images showed that both agents caused rapid fusion of newcomer insulin granules with ... Read More »
» Published in Diabetes. 2006 Oct;55(10):2819-25.

9. Insulin resistance and increased pancreatic beta-cell proliferation in mice expressing a mutant insulin receptor (P1195L).
Match Strength: 5.415

Several mutations of the tyrosine kinase domain of insulin receptor (IR) have been clinically reported to lead insulin resistance and insulin hypersecretion in humans. However, it has not been completely clarified how insulin resistance and pancreatic beta-cell function affect each other under the expression of mutant IR. We investigated the response of pancreatic beta-cells in mice carrying a mutation (P1195L) in the tyrosine kinase domain of IR beta-subunit. Homozygous (Ir(P1195L/P1195L)) mice showed severe ketoacidosis and died within 2 days after birth, and heterozygous (Ir(P1195L/wt)) ... Read More »
» Published in J Endocrinol. 2006 Sep;190(3):739-47.

10. Effect of switching medically vulnerable patients with uncontrolled diabetes from isophane insulin human to insulin glargine.
Match Strength: 5.410

PURPOSE: The purpose of this observational study was to determine if switching from isophane insulin human (NPH) to insulin glargine would improve glycemic control in a medically vulnerable population with uncontrolled diabetes. METHODS: A retrospective cohort review of patients' medical records was performed that recorded events occurring between January 1, 2001, and December 31, 2003. The cohort consisted of patients with diabetes in an adult medicine clinic at a county hospital. Patients were included if they were receiving NPH insulin for a minimum of six months and subsequently switched ... Read More »
» Published in Am J Health Syst Pharm. 2006 Oct 1;63(19):1862-71.

11. Actions of glucagon-like peptide-1 on KATP channel-dependent and -independent effects of glucose, sulphonylureas and nateglinide.
Match Strength: 5.378

This study examined the effects of glucagon-like peptide-1 (GLP-1) on insulin secretion alone and in combination with sulphonylureas or nateglinide, with particular attention to K(ATP) channel-independent insulin secretion. In depolarised cells, GLP-1 significantly augmented glucose-induced K(ATP) channel-independent insulin secretion in a glucose concentration-dependent manner. GLP-1 similarly augmented the K(ATP) channel-independent insulin-releasing effects of tolbutamide, glibenclamide or nateglinide. Downregulation of protein kinase A (PKA)- or protein kinase C (PKC)-signalling pathways ... Read More »
» Published in J Endocrinol. 2006 Sep;190(3):889-96.

12. Impact of defined matrix interactions on insulin production by cultured human beta-cells: effect on insulin content, secretion, and gene transcription.
Match Strength: 5.376

The impact of extracellular matrix on insulin production needs to be understood both to optimize the derivation of functional beta-cells for transplantation and to understand mechanisms controlling islet neogenesis and glucose homeostasis. In this study, we present evidence that adhesion to some common matrix constituents has a profound impact on the transcription, secretion, and storage of insulin by human beta-cells. The integrin-dependent adhesion of fetal beta-cells to both collagen IV and vitronectin induces significant glucose-independent insulin secretion and a substantial reciprocal ... Read More »
» Published in Diabetes. 2006 Oct;55(10):2723-9.

13. Characterization of insulin secretion in Valproate-treated patients with epilepsy.
Match Strength: 5.316

PURPOSE: Valproate (VPA) treatment has been reported to be associated with obesity and high fasting serum insulin concentrations in parallel with an unfavorable serum lipid profile and hyperandrogenism and polycystic ovaries in women. The pathogenetic mechanism underlying these changes has remained unknown, although several mechanisms have been implicated. METHODS: Fifty-one patients receiving monotherapy (31 male and 20 female patients) were included in this study, with 45 (23 male and 22 female) healthy control subjects. These participants were interviewed, clinically examined, and blood ... Read More »
» Published in Epilepsia. 2006 Sep;47(9):1460-4.

14. Activation of the extracellular calcium-sensing receptor initiates insulin secretion from human islets of Langerhans: involvement of protein kinases.
Match Strength: 5.269

The extracellular calcium-sensing receptor (CaR) is usually associated with systemic Ca(2+) homeostasis, but the CaR is also expressed in many other tissues, including pancreatic islets of Langerhans. In the present study, we have used human islets and an insulin-secreting cell line (MIN6) to investigate the effects of CaR activation using the calcimimetic R-568, a CaR agonist that activates the CaR at physiological concentrations of extracellular Ca(2+). CaR activation initiated a marked but transient insulin secretory response from both human islets and MIN6 cells at a sub-stimulatory ... Read More »
» Published in J Endocrinol. 2006 Sep;190(3):703-10.

15. Hereditary postprandial hypertriglyceridemic rabbit exhibits insulin resistance and central obesity: a novel model of metabolic syndrome.
Match Strength: 5.069

OBJECTIVE: We have established a hereditary postprandial hypertriglyceridemic (PHT) rabbit. The present study was designed to define whether this rabbit model represents both insulin resistance and central obesity. METHODS AND RESULTS: Body weight, abdominal circumference, visceral fat weight, and glucose tolerance were compared between PHT and Japanese white (JW) rabbit. Plasma levels of triglycerides (TG), total cholesterol (TC), glucose, and insulin were measured before and after feeding. Abdominal circumference of PHT rabbit was larger than that of JW rabbit, with no difference in body ... Read More »
» Published in Arterioscler Thromb Vasc Biol. 2006 Dec;26(12):2752-7. Epub 2006 Sep 21.

16. The effect of insulin infusion upon protein metabolism in neonates on extracorporeal life support.
Match Strength: 5.042

OBJECTIVE: Critically ill neonates on extracorporeal life support (ECLS) demonstrate elevated rates of protein breakdown that, in turn, are associated with increased morbidity and mortality. This study sought to determine if the administration of the anabolic hormone insulin improved net protein balance in neonates on ECLS. METHODS: Twelve parenterally fed neonates, on ECLS, were enrolled in a randomized, prospective, crossover trial. Subjects were administered a hyperinsulinemic euglycemic clamp and a control saline infusion. Protein metabolism was quantified using ring-D5-phenylyalanine and ... Read More »
» Published in Ann Surg. 2006 Oct;244(4):536-44.

17. Prevention of hypoglycemia during exercise in children with type 1 diabetes by suspending basal insulin.
Match Strength: 5.025

OBJECTIVE: Strategies for preventing hypoglycemia during exercise in children with type 1 diabetes have not been well studied. The Diabetes Research in Children Network (DirecNet) Study Group conducted a study to determine whether stopping basal insulin could reduce the frequency of hypoglycemia occurring during exercise. RESEARCH DESIGN AND METHODS: Using a randomized crossover design, 49 children 8-17 years of age with type 1 diabetes on insulin pump therapy were studied during structured exercise sessions on 2 days. On day 1, basal insulin was stopped during exercise, and on day 2 it was ... Read More »
» Published in Diabetes Care. 2006 Oct;29(10):2200-4.

18. Randomized Study to Characterize Glycemic Control and Short-Term Pulmonary Function in Patients with Type 1 Diabetes Receiving Inhaled Human Insulin (Exubera(R)).
Match Strength: 4.895

OBJECTIVE: Previous studies with inhaled human insulin (INH; Exubera((R)); (insulin human [rDNA origin]) Inhalation Powder) show comparable efficacy to sc insulin and small declines in pulmonary function in type 1 or 2 diabetes. This is a detailed characterization of efficacy and short-term pulmonary safety profile of INH. RESEARCH DESIGN AND METHODS: In a 24-week multicenter study, 226 nonsmoking patients with type 1 diabetes and normal lung function were randomized to premeal INH or SC insulin for 12 weeks (comparative phase), followed by SC insulin for 12 weeks (washout phase). HbA1c was ... Read More »
» Published in J Clin Endocrinol Metab. 2006 Sep 26;

19. Management of diabetes mellitus in hospitalized patients: efficiency and effectiveness of sliding-scale insulin therapy.
Match Strength: 4.888

STUDY OBJECTIVE: To determine the efficiency and effectiveness of current prescribing practices relative to short- and intermediate-acting insulins in the prevention or treatment of acute hyperglycemic episodes in hospitalized patients with diabetes mellitus or hyperglycemia, and to identify clinical findings that influence the effectiveness of insulin therapy in these patients. DESIGN: Retrospective observational study. SETTING: University-affiliated hospital. PATIENTS: Ninety consecutive adult inpatients who had orders placed for as-needed subcutaneous regular or lispro sliding-scale insulin ... Read More »
» Published in Pharmacotherapy. 2006 Oct;26(10):1421-32.

20. A double-blind, placebo-controlled trial assessing pramlintide treatment in the setting of intensive insulin therapy in type 1 diabetes.
Match Strength: 4.888

OBJECTIVE: To assess safety, efficacy, and tolerability of pramlintide dose escalation with proactive mealtime insulin reduction, followed by insulin optimization, in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: This 29-week, double-blind, placebo-controlled study randomized 296 patients to pramlintide or placebo as an adjunct to insulin. During initiation, pramlintide was escalated from 15 to 60 microg/meal (15-microg increments) with recommended reductions (30-50%) in mealtime insulin. Insulin was subsequently adjusted to optimize glycemic control. End points included safety ... Read More »
» Published in Diabetes Care. 2006 Oct;29(10):2189-95.

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