Abstract:
:Cyclic nucleotide phosphodiesterase (PDE) 3B plays an important role in the antilipolytic action of insulin and, thereby, the release of fatty acids from adipocytes. Increased concentrations of circulating fatty acids as a result of elevated or unrestrained lipolysis cause insulin resistance. The lipolytic action of tumor necrosis factor (TNF)-alpha is thought to be one of the mechanisms by which TNF-alpha induces insulin resistance. Ceramide is the suggested second messenger of TNF-alpha action, and in this study, we used 3T3-L1 adipocytes to investigate the effects of C(2)-ceramide (a short-chain ceramide analog) on the expression and regulation of PDE3B and lipolysis. Incubation of adipocytes with 100 micromol/l C(2)-ceramide (N-acetyl-sphingosine) resulted in a time-dependent decrease of PDE3B activity, accompanied by decreased PDE3B protein expression. C(2)-ceramide, in a time- and dose-dependent manner, stimulated lipolysis, an effect that was blocked by H-89, an inhibitor of protein kinase A. These ceramide effects were prevented by 20 micromol/l troglitazone, an antidiabetic drug. In addition to downregulation of PDE3B, the antilipolytic action of insulin was decreased by ceramide treatment. These results, together with data from other studies on PDE3B and lipolysis in diabetic humans and animals, suggest a novel pathway by which ceramide induces insulin resistance. Furthermore, PDE3B is demonstrated to be a target for troglitazone action in adipocytes.
journal_name
Diabetesjournal_title
Diabetesauthors
Mei J,Holst LS,Landström TR,Holm C,Brindley D,Manganiello V,Degerman Edoi
10.2337/diabetes.51.3.631subject
Has Abstractpub_date
2002-03-01 00:00:00pages
631-7issue
3eissn
0012-1797issn
1939-327Xjournal_volume
51pub_type
杂志文章相关文献
DIABETES文献大全abstract::Type 1 diabetes appears to progress not as an uncontrolled autoimmune attack on the pancreatic islet beta-cells, but rather in a highly regulated manner. Leukocytic infiltration of the pancreatic islets by autoimmune cells, or insulitis, can persist for long periods of time before the terminal destruction of beta-cell...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.9.2310
更新日期:2004-09-01 00:00:00
abstract::This study assessed the site of increased glucose uptake resulting from insulin inhalation, quantified its effect under steady-state glucose concentrations, and identified the time to onset of effect. Human insulin was administered to 13 beagles via inhalation (Exubera [insulin human (rDNA origin)] Inhalation Powder; ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-0718
更新日期:2006-12-01 00:00:00
abstract::We describe an automated method for the isolation of human pancreatic islets. The procedure meets the following requirements: 1) minimal traumatic action on the islets, 2) continuous digestion in which the islets that are progressively liberated can be saved from further enzymatic action, 3) minimal human intervention...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.37.4.413
更新日期:1988-04-01 00:00:00
abstract::Although epinephrine stimulates insulin release by activation of beta-adrenergic receptors, its dominant effect (mediated by stimulation of alpha-adrenergic receptors) is an inhibition of insulin secretion that is powerful enough to suppress the secretory activity of insulin's most potent stimulants. The insulin-secre...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.27.5.550
更新日期:1978-05-01 00:00:00
abstract::The effects of elevated EPI and CORT levels on KG, SI, and SG were studied in dogs with alloxan-induced diabetes. Conscious dogs received SAL, EPI 20 ng.kg-1.min-1 for 30 min (short EPI) or 72 h (long EPI), or CORT 200 micrograms.kg-1.min-1 for 60 min (short CORT) or 72 h (long CORT) before assessment of glucose metab...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.41.11.1446
更新日期:1992-11-01 00:00:00
abstract::Alzheimer disease and type 2 diabetes are characterized by increased prevalence with aging, a genetic predisposition, and comparable pathological features in the islet and brain (amyloid derived from amyloid beta protein in the brain in Alzheimer disease and islet amyloid derived from islet amyloid polypeptide in the ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.2.474
更新日期:2004-02-01 00:00:00
abstract::The peripheral nerve disorders associated with diabetes are complex and probably involve a variety of causative mechanisms. This may give rise to difficulty in the classification of individual cases. A broad separation into rapidly reversible or more persistent phenomena is helpful. The former, which can be categorize...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diab.46.2.s54
更新日期:1997-09-01 00:00:00
abstract::Incubation of 3T3-L1 adipocytes with C2- and C6-ceramides (N-acetyl- and N-hexanoylsphingosines) but not dihydro-C2-ceramide increased 2-deoxyglucose uptake in the absence of insulin. This effect was inhibited by PD 98059, LY 294002, and rapamycin, which block the activation of mitogen-activated protein kinase, phosph...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.47.1.24
更新日期:1998-01-01 00:00:00
abstract::Concentrations of glycosylated hemoglobin (GHb) are elevated in diabetes mellitus and are believed to reflect previous metabolic control. To better define possible determinants of GHb in man, we investigated the relationship between GHb and both fasting plasma glucose (FPG) and basal insulin (IRI) in 42 normal subject...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.27.8.834
更新日期:1978-08-01 00:00:00
abstract::In type 1 diabetes, a lifelong autoimmune disease, T cells infiltrate the islets and the exocrine pancreas in high numbers. CD8+ T cells are the main cell type found in the insulitic lesion, and CD8+ T cells reactive against beta cell antigens have been detected in the periphery and in the pancreas of subjects with sh...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db20-0908
更新日期:2021-01-07 00:00:00
abstract::Glucokinase is a critical component of the physiological glucose sensor found in cell types that are responsive to changes in plasma glucose levels. The acute regulation of glucokinase activity has been shown to occur via a regulatory protein found in liver parenchymal cells (Van Schaftingen E, Detheux M, Da Cunha MV....
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.45.12.1670
更新日期:1996-12-01 00:00:00
abstract::The effect of maternal diabetes on teratogenesis was examined utilizing female Chinese hamsters with typical diabetic symptoms from our closed colony (CHA) and F13-F19 of the brother-sister mating generations of a diabetic strain (CHAD). Both groups were mated with nondiabetic males from CHA. Embryologic studies on da...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.32.7.637
更新日期:1983-07-01 00:00:00
abstract::In an ongoing investigation of the effects of age on G protein-coupled receptor signaling in human atrial tissue, we have found that the density of atrial muscarinic acetylcholine receptor (mAChR) increases with age but reaches statistical significance only in patients with diabetes. Moreover, we find that in elderly ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.53.9.2392
更新日期:2004-09-01 00:00:00
abstract::Nine offspring of two diabetic parents and 18 normals were studied with two intravenous glucose loads (o.5 gm./kg. body weight), 60 minutes apart. By thus stressing the beta cell, subtle defects could be identified in the prediabetics: (1) An inverse relationship between insulin peak response and insulin concentration...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.26.12.1184
更新日期:1977-12-01 00:00:00
abstract::Diabetes is characterized by altered metabolism of key molecules and regulatory pathways. The phenotypic expression of diabetes and associated complications encompasses complex interactions between genetic, environmental, and tissue-specific factors that require an integrated understanding of perturbations in the netw...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/db14-0509
更新日期:2015-03-01 00:00:00
abstract::The isolated rat liver perfused for 12 hours at pH 7.10 with a suspension of bovine erythrocytes in Krebs-Ringer bicarbonate buffer containing 3 per cent bovine serum albumin has been used as a test system to study effects of glucagon and of dexamethasone in the presence and absence of insulin on net biosynthesis of r...
journal_title:Diabetes
pub_type: 杂志文章
doi:
更新日期:1976-01-01 00:00:00
abstract::We reported earlier that β-cell-specific overexpression of glutathione peroxidase (GPx)-1 significantly ameliorated hyperglycemia in diabetic db/db mice and prevented glucotoxicity-induced deterioration of β-cell mass and function. We have now ascertained whether early treatment of Zucker diabetic fatty (ZDF) rats wit...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db13-0357
更新日期:2013-10-01 00:00:00
abstract::Diabetic hearts exhibit decreased responsiveness to stimulation by beta-adrenoreceptor (beta-AR) agonists. This decrease in activity may be due to changes in expression and/or signaling of beta-AR. Recently we showed that right atrial strips from 14-week streptozotocin (STZ)-induced diabetic rat hearts exhibit decreas...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.50.2.455
更新日期:2001-02-01 00:00:00
abstract::Specific binding of [3H]SCH 23390 to dopamine D1 receptors in the striatum and olfactory tubercle in 14-day alloxan-induced diabetic rats was investigated. The Scatchard analysis revealed decreased D1 receptor density in the striatum (Bmax values were 548 +/- 23 fmol/mg protein for the control and 466 +/- 33 fmol/mg f...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.41.9.1119
更新日期:1992-09-01 00:00:00
abstract::Transgenic mice expressing the amyloidogenic human islet amyloid polypeptide (hIAPP) in their islet beta-cells are a model of islet amyloid formation as it occurs in type 2 diabetes. Our hIAPP transgenic mice developed islet amyloid when fed a breeder chow but not regular chow. Because the breeder chow contained incre...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.2.372
更新日期:2003-02-01 00:00:00
abstract::Retrospective studies of patients with non-insulin-dependent diabetes mellitus (NIDDM) have suggested that microalbuminuria predicts early all-cause (mainly cardiovascular) mortality independently of arterial blood pressure. These findings have not been confirmed in prospective studies, and it is not known whether the...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.41.6.736
更新日期:1992-06-01 00:00:00
abstract::Growing evidence suggests that epigenetic profile changes occurring during fetal development in response to in utero environment variations could be one of the mechanisms involved in the early determinants of adult chronic diseases. In this study, we tested whether maternal glycemic status is associated with the adipo...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db11-1160
更新日期:2012-05-01 00:00:00
abstract::The strategy of positional cloning has been highly successful in identifying a number of single gene disorders that exhibit clear Mendelian patterns of inheritance. Positional cloning of insulin-dependent diabetes mellitus (IDDM) has been assisted by the expansion of molecular genetic tools and highly informative mark...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.44.2.139
更新日期:1995-02-01 00:00:00
abstract::Elevation of glucagon levels and increase in α-cell mass are associated with states of hyperglycemia in diabetes. Our previous studies have highlighted the role of nutrient signaling via mTOR complex 1 (mTORC1) regulation that controls glucagon secretion and α-cell mass. In the current studies we investigated the effe...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db20-0440
更新日期:2021-02-01 00:00:00
abstract::The Edwin Bierman Award Lecture is presented in honor of the memory of Edwin L. Bierman, MD, an exemplary scientist, mentor, and leader in the field of diabetes, obesity, hyperlipidemia, and atherosclerosis. The award and lecture recognizes a leading scientist in the field of macrovascular complications and contributi...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/db16-0152
更新日期:2016-06-01 00:00:00
abstract::The N6-methyladenosine (m6A) RNA modification is essential during embryonic development of various organs. However, its role in embryonic and early postnatal islet development remains unknown. Mice in which RNA methyltransferase-like 3/14 (Mettl3/14) were deleted in Ngn3+ endocrine progenitors (Mettl3/14 ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db19-0906
更新日期:2020-08-01 00:00:00
abstract::To investigate whether insulin reduces platelet aggregability through a modulation of the guanosine-3',5'-cyclic monophosphate (cGMP) concentrations, we determined by a radioimmunoassay the cGMP values in the platelet-rich plasma (PRP) obtained from 17 healthy volunteers and incubated for 3 min with different concentr...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.43.8.1015
更新日期:1994-08-01 00:00:00
abstract::The paucity of animal models exhibiting full pathology of diabetic retinopathy (DR) has impeded understanding of the pathogenesis of DR and the development of therapeutic interventions. Here, we investigated whether hyperhexosemic marmosets (Callithrix jacchus) develop characteristic retinal vascular lesions including...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db14-0866
更新日期:2015-07-01 00:00:00
abstract:OBJECTIVE:Recent studies in humans and animal models of obesity have shown increased adipose tissue activity of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which amplifies local tissue glucocorticoid concentrations. The reasons for this 11beta-HSD1 dysregulation are unknown. Here, we tested whether 11beta...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-0873
更新日期:2009-12-01 00:00:00
abstract::Müller cells and macrophages/microglia are likely important for the development of diabetic retinopathy; however, the interplay between these cells in this disease is not well understood. An inflammatory process is linked to the onset of experimental diabetic retinopathy. CD40 deficiency impairs this process and preve...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-0051
更新日期:2017-02-01 00:00:00