Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of schizophrenia with olanzapine and other atypical antipsychotic agents is associated with insulin resistance and diabetes mellitus. The mechanism for this is not understood. Adiponectin is an insulin-sensitizing cytokine secreted by adipocytes. It is present in serum in multimers of varying size. Trimers and hexamers are referred to as low molecular weight (LMW) adiponectin. Larger multimers (12-, 18-, and 24-mers) have been designated high molecular weight (HMW) adiponectin and seem responsible for the insulin-sensitizing action of this adipokine. The aim of this study was to examine total adiponectin and LMW and HMW multimers in serum from patients with schizophrenia treated with either olanzapine (n = 9) or other typical antipsychotics (n = 9) and compare results with 16 healthy sex-, body mass index-, and age-matched controls. The effects of olanzapine on adiponectin protein expression and secretion in in vitro-differentiated primary human adipocytes were also examined. Patients receiving olanzapine had significantly lower total serum adiponectin as compared with those on conventional treatment and controls (5.23 +/- 1.53 ng/mL vs. 8.20 +/- 3.77 ng/mL and 8.78 +/- 3.8 ng/mL; P < 0.05 and P < 0.01, respectively). The HMW adiponectin was also reduced in patients on olanzapine as compared with the disease and healthy control groups (1.67 +/- 0.96 ng/mL vs. 3.87 +/- 2.69 ng/mL and 4.07 +/- 3.2 ng/mL; P < 0.05 for both). The LMW adiponectin was not different between patient groups (P = 0.15) but lower in patients on olanzapine as compared with controls (3.56 +/- 0.85 ng/mL vs. 4.70 +/- 1.4 ng/mL; P < 0.05). In vitro, short duration (up to 7 days) olanzapine exposure had no effect on total adiponectin expression or multimer composition of secreted protein. In summary, this study demonstrates a correlation between olanzapine treatment and reduced serum adiponectin, particularly HMW multimers. This may not be a direct effect of olanzapine on adipocyte expression or secretion of adiponectin. These observations provide insights into possible mechanisms for the association between olanzapine treatment and insulin resistance.
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PMID:Olanzapine treatment is associated with reduced high molecular weight adiponectin in serum: a potential mechanism for olanzapine-induced insulin resistance in patients with schizophrenia. 1670 87

Adiponectin (APM1) is an adipocyte-derived peptide that contributes to glucose, lipid, and energy homeostasis. We assessed the genetic basis of plasma adiponectin in Hispanic-American and African-American families enrolled through the Insulin Resistance Atherosclerosis Study Family Study. A 10-cM genome scan was performed in two batches: an original set (set 1) consisting of 66 families (45 Hispanic American and 21 African American) and a replication set (set 2) consisting of 66 families (45 Hispanic American and 21 African American). Adiponectin levels were measured by radioimmunoassay in 1,727 individuals from 131 of 132 families. Linkage analysis was carried out in Hispanic Americans and African Americans separately in set 1, set 2, and the pooled set (set 1 plus set 2), with and without diabetic subjects. A major gene was mapped to 3q27 with a logarithm of odds (LOD) score of 8.21 in the Hispanic-American sample. Ninety-six unrelated individuals were screened for polymorphisms in the APM1 gene, and 18 single nucleotide polymorphisms (SNPs) were genotyped in the Hispanic-American sample. Plasma adiponectin level was modestly associated with two SNPs and their accompaning haplotypes. Incorporating each or both SNPs in the linkage analysis, however, did not significantly reduce the LOD score. Therefore, a quantitative trait locus at 3q27, likely distinct from the APM1 gene, contributes to the variation of plasma adiponectin levels in the Hispanic-American population.
Diabetes 2006 Jun
PMID:Genome-wide linkage of plasma adiponectin reveals a major locus on chromosome 3q distinct from the adiponectin structural gene: the IRAS family study. 1673 35

Adiponectin is an abundant adipocyte-derived plasma protein with antiatherosclerotic effects. Vascular signal transduction by adiponectin is poorly understood and may involve 5'-AMP-activated protein kinase (AMPK), cAMP signaling, and other pathways. Hyperglycemia sharply increases the production of reactive oxygen species (ROS), which play a key role in endothelial dysfunction in diabetes. Because the recombinant globular domain of human adiponectin (gAd) reduces the generation of endothelial ROS induced by oxidized LDL, we sought to determine whether adiponectin could also suppress ROS production induced by high glucose in cultured human umbilical vein endothelial cells. Incubation in 25 mmol/l glucose for 16 h increased ROS production 3.8-fold (P<0.05), using a luminol assay. Treatment with gAd for 16 h suppressed glucose-induced ROS in a dose-dependent manner up to 81% at 300 nmol/l (P<0.05). The AMPK activator 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR; 1 mmol/l, 16 h) only partially decreased glucose-induced ROS by 22% (P<0.05). Cell pretreatment with AMPK inhibitors, however, failed to block the effect of gAd to suppress glucose-induced ROS, suggesting that the action of gAd was independent of AMPK. Interestingly, activation of cAMP signaling by treatment with forskolin (2 micromol/l) or dibutyryl-cAMP (0.5 mmol/l) reduced glucose-induced ROS generation by 43 and 67%, respectively (both P<0.05). Incubation with the cAMP-dependent protein kinase (PKA) inhibitor H-89 (1 micromol/l) fully abrogated the effect of gAd, but not that of AICAR, on ROS induced by glucose. gAd also increased cellular cAMP content by 70% in an AMPK-independent manner. Full-length adiponectin purified from a eukaryotic expression system also suppressed ROS induced by high glucose or by treatment of endothelial cells with oxidized LDL. Thus, adiponectin suppresses excess ROS production under high-glucose conditions via a cAMP/PKA-dependent pathway, an effect that has implications for vascular protection in diabetes.
Diabetes 2006 Jun
PMID:Adiponectin suppression of high-glucose-induced reactive oxygen species in vascular endothelial cells: evidence for involvement of a cAMP signaling pathway. 1673 51

This study was designed to examine the association between adiponectin and C-reactive protein (CRP), interleukin-6 (IL-6) and endothelin-1, (ET-1) and their possible role in prediction of type-2 diabetes and development of diabetes and macrovascular complications. Forty subjects were studied. They were classified into four equal groups: Control, newly diagnosed type-2 diabetes, diabetics with old myocardial infarction (OMI) and acute myocardial infarction (AMI) groups. They were matched for body mass index (BMI), age, and sex. Adiponectin and IL-6 were determined by ELISA technique, CRP was determined by immunonephlometry and ET-1 was determined by radioimmunoassay. Adiponectin was found to be decreased in newly diagnosed diabetics (6.64 +/- 2.3 microg/ml), OMI (4.7 +/- 1.05 microg/ml) and AMI (4.23 +/- 0.73 microg/ml) when compared to controls (9.81 +/- 2.2 microg/ml), whereas CRP, IL- 6 and ET-1 were significantly elevated in AMI (18.6 +/- 5.3 mg/l, 12.6 +/- 4.2 pg/ml and 36.8 +/- 10.4 fmol/ml, respectively). The changes were marked in AMI group compared to other diabetic groups. Only adiponectin significantly decreased in newly diagnosed type-2 diabetics, but CRP, IL-6 and ET-1 did not significantly altered in newly diagnosed diabetics (4.9 +/- 1.6 mg/l, 6.9 +/- 2.3 pg/ml and 22.1 +/- 8.6 fmol/ml, respectively) compared to control. Adiponectin correlated negatively with CRP, IL-6 and ET-1, BMI and HbA1c, whereas inflammatory and vascular markers correlated positively with each other and with BMI and HbA1c. In conclusions, adiponectin may be implicated in the development of type-2 diabetes and macrovascular complications and can be used as an early predictor of type-2 diabetes. Whereas, none of the inflammatory and vascular markers can predict diabetes, but can be used as markers of acute vascular events and in follow up of these cases. Immunomodulation of adiponectin may help prevention and treatment of type-2 diabetes and its complications.
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PMID:Adiponectin and some inflammatory and endothelial markers in type-2 diabetes with and without cardiovascular disease. 1673 48

The paper reviews the structure and role of adiponectin in the regulation of metabolic balance. Adiponectin is the most abundant adipocytokine that is produced exclusively in the fat tissue. Its high concentration protects from diabetes mellitus, atherosclerosis and insulin resistance, its low concentration increases the risk of these disorders. The adiponectin gene is one of the many candidate genes in type 2 diabetes. Adiponectin binds to two types of receptors: 1 and 2, encoded by two genes: AdipoR1, and AdipoR2, respectively. The receptors are found in all tissues, with type 1 predominant in the muscles, and type 2 in the liver. Most importantly, the role of adiponectin in the body and the results of animal model experiments suggest the possible future use of adiponectin in the treatment of diabetes, atherosclerosis and obesity.
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PMID:[Adiponectin and its role in the pathogenesis of obesity, diabetes mellitus and insulin resistance]. 1678 Feb 74

Adiponectin (Acrp30), an adipocyte-derived protein, exists in serum as a trimer, a hexamer, and a high-molecular weight (HMW) form, including 12-18 subunits. Because HMW adiponectin may be biologically active, we measured it in serum using a novel enzyme-linked immunosorbent assay (ELISA) confirmed by gel filtration chromatography that the ELISA detected mainly adiponectin with 12-18 subunits, and we compared HMW with total adiponectin concentration in patients with type 2 diabetes. We next investigated the relationship between serum HMW and coronary artery disease (CAD) in 280 consecutive type 2 diabetic patients, including 59 patients with angiographically confirmed CAD. Total adiponectin was measured in serum by a commercially available ELISA. Like serum total adiponectin, HMW adiponectin correlated positively with HDL cholesterol and negatively with triglyceride, insulin sensitivity, creatinine clearance, and circulating inflammatory markers. Total and HMW adiponectin were significantly higher in women than in men, as was the HMW-to-total adiponectin ratio. Serum HMW and the HMW-to-total adiponectin ratio were significantly lower in men with than without CAD (P < 0.05, respectively). In women, the ratio, but neither total nor HMW adiponectin, tended to be lower when CAD was present. In conclusion, determination of HMW adiponectin, especially relative to total serum adiponectin, is useful for evaluating CAD in type 2 diabetic patients.
Diabetes 2006 Jul
PMID:Comparison of serum high-molecular weight (HMW) adiponectin with total adiponectin concentrations in type 2 diabetic patients with coronary artery disease using a novel enzyme-linked immunosorbent assay to detect HMW adiponectin. 1680 63

Adiponectin, an adipocyte secretory hormone, has been causally linked to insulin resistance in the metabolic syndrome and diabetes. A recent paper (Mao et al., 2006) shows that the APPL1 adaptor protein binds to the intracellular domain of adiponectin receptors and mediates some of adiponectin's actions, identifying a novel mechanism linking adiponectin to insulin sensitization.
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PMID:APPLied mechanics: uncovering how adiponectin modulates insulin action. 1681 26

Adiponectin is an adipokine that is specifically and abundantly expressed in adipose tissue and directly sensitizes the body to insulin. Hypoadiponectinemia, caused by interactions of genetic factors such as SNPs in the Adiponectin gene and environmental factors causing obesity, appears to play an important causal role in insulin resistance, type 2 diabetes, and the metabolic syndrome, which are linked to obesity. The adiponectin receptors, AdipoR1 and AdipoR2, which mediate the antidiabetic metabolic actions of adiponectin, have been cloned and are downregulated in obesity-linked insulin resistance. Upregulation of adiponectin is a partial cause of the insulin-sensitizing and antidiabetic actions of thiazolidinediones. Therefore, adiponectin and adiponectin receptors represent potential versatile therapeutic targets to combat obesity-linked diseases characterized by insulin resistance. This Review describes the pathophysiology of adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome.
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PMID:Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. 1682 76

Adiponectin is a plasma protein derived from adipose tissue, which we discovered from a human adipose cDNA project. Adiponectin exists in circulating plasma at concentrations ranging from 4 to 30 microg/mL, which is much higher than the concentrations of various other hormones and cytokines. Adiponectin has a sticky nature, binding to collagen I, III, and V, which are present in vascular intima. Adiponectin exhibits various antiatherogenic effects on vascular cells, suppressing the expression of adhesion molecules in vascular endothelial cells, proliferation of smooth muscle cells, and cholesteryl-ester accumulation in macrophages. However, its plasma levels are low in subjects with excess intra-abdominal fat. Adiponectin also has antidiabetic properties, and plasma adiponectin levels correlate positively with insulin sensitivity. Several clinical studies have demonstrated that hypoadiponectinemia is a risk factor for new-onset diabetes. Recent studies suggest that hypoadiponectinemia may partly contribute to the development of salt-sensitive hypertension and hypertensive heart failure, and can be also a risk factor for overnutrition-related cancers such as breast, colon, uterine, and prostate cancers. Hypoadiponectinemia might be at least in part the molecular basis of various diseases associated with overnutrition.
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PMID:Hypoadiponectinemia: a common basis for diseases associated with overnutrition. 1690 15

Obesity is a major health problem in cats and a risk factor for diabetes. It has been postulated that cats are always gluconeogenic and that the rise in obesity might be related to high dietary carbohydrates. We examined the effect of a high-carbohydrate/low-protein (HC) and a high-protein/low-carbohydrate (HP) diet on glucose and fat metabolism during euglycemic hyperinsulinemic clamp, adipocytokines, and fat distribution in 12 lean and 16 obese cats before and after weight loss. Feeding diet HP led to greater heat production in lean but not in obese cats. Regardless of diet, obese cats had markedly decreased glucose effectiveness and insulin resistance, but greater suppression of nonesterified fatty acids during the euglycemic hyperinsulinemic clamp was seen in obese cats on diet HC compared with lean cats on either diet or obese cats on diet HP. In contrast to humans, obese cats had abdominal fat equally distributed subcutaneously and intra-abdominally. Weight loss normalized insulin sensitivity; however, increased nonesterified fatty acid suppression was maintained and fat loss was less in cats on diet HC. Adiponectin was negatively and leptin positively correlated with fat mass. Lean cats and cats during weight loss, but not obese cats, adapted to the varying dietary carbohydrate/protein content with changes in substrate oxidation. We conclude that diet HP is beneficial through maintenance of normal insulin sensitivity of fat metabolism in obese cats, facilitating the loss of fat during weight loss, and increasing heat production in lean cats. These data also show that insulin sensitivity of glucose and fat metabolism can be differentially regulated in cats.
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PMID:Insulin sensitivity, fat distribution, and adipocytokine response to different diets in lean and obese cats before and after weight loss. 1690 86


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