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Gamma Isoform (gamma + isoform)

Distribution by Scientific Domains

Medical Sciences	50%
Life Sciences	50%

Selected Abstracts

The mode of action of thiazolidinediones,

DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue S2 2002
Hans Hauner
Abstract The thiazolidinediones (TZDs) or ,glitazones' are a new class of oral antidiabetic drugs that improve metabolic control in patients with type 2 diabetes through the improvement of insulin sensitivity. TZDs exert their antidiabetic effects through a mechanism that involves activation of the gamma isoform of the peroxisome proliferator-activated receptor (PPAR,), a nuclear receptor. TZD-induced activation of PPAR, alters the transcription of several genes involved in glucose and lipid metabolism and energy balance, including those that code for lipoprotein lipase, fatty acid transporter protein, adipocyte fatty acid binding protein, fatty acyl-CoA synthase, malic enzyme, glucokinase and the GLUT4 glucose transporter. TZDs reduce insulin resistance in adipose tissue, muscle and the liver. However, PPAR, is predominantly expressed in adipose tissue. It is possible that the effect of TZDs on insulin resistance in muscle and liver is promoted via endocrine signalling from adipocytes. Potential signalling factors include free fatty acids (FFA) (well-known mediators of insulin resistance linked to obesity) or adipocyte-derived tumour necrosis factor-, (TNF-,), which is overexpressed in obesity and insulin resistance. Although there are still many unknowns about the mechanism of action of TZDs in type 2 diabetes, it is clear that these agents have the potential to benefit the full ,insulin resistance syndrome' associated with the disease. Therefore, TZDs may also have potential benefits on the secondary complications of type 2 diabetes, such as cardiovascular disease. Copyright © 2002 John Wiley & Sons, Ltd. [source]

Deficits in the mid-brain raphe nuclei and striatum of the AS/AGU rat, a protein kinase C-, mutant

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2005
M. Al-Fayez
Abstract The AS/AGU rat carries a recessive mutation (agu) in the gene coding for the gamma isoform of protein kinase C. The rat is characterized by disordered locomotion and progressive dysfunction of the nigrostriatal dopaminergic (DA) system. This dysfunction begins with a failure to release DA within the striatum and culminates in cell loss within the substantia nigra pars compacta. The present study examines another midbrain aminergic system with input to the basal ganglia, the serotonergic (5-HT) raphe,striatal system originating in the dorsal raphe nucleus. By 3 months after birth, there is a very substantial reduction in the extracellular levels of 5-HT in the dorsal caudate-putamen of the mutants compared with controls (c. 70%). This is accompanied by a proportional increase in the levels of the 5-HT metabolite 5-hydroxyindole acetic acid (5-HIAA). At a later age, there are reductions in whole tissue 5-HT (and increases in 5-HIAA) in both the striatum and the region containing the dorsal raphe nucleus, as well as numbers of 5-HT-immunoreactive cells in the dorsal raphe nucleus. The median raphe appears to be unaffected. The results are seen in terms of an initial dysfunction in transmitter release leading to cell death, perhaps through the formation of free radicals or neurotoxins. [source]

Regulation of protein phosphatase 1, activity in hypoxia through increased interaction with NIPP1: Implications for cellular metabolism

JOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2006
Kathrina M. Comerford
Eukaryotic cells sense decreased oxygen levels and respond by altering their metabolic strategy to sustain non-respiratory ATP production through glycolysis, and thus promote cell survival in a hypoxic environment. Protein phosphatase 1 (PP1) has been recently implicated in the governance of the rational use of energy when metabolic substrates are abundant and contributes to cellular recovery following metabolic stress. Under conditions of hypoxia, the expression of the gamma isoform of PP1 (PP1,), is diminished, an event we have hypothesized to be involved in the adaptive cellular response to hypoxia. Decreased PP1, activity in hypoxia has a profound impact on the activity of the cAMP response element binding protein (CREB), a major transcriptional regulator of metabolic genes and processes. Here, we demonstrate a further mechanism leading to inhibition of PP1 activity in hypoxia which occurs at least in part through increased association with the nuclear inhibitor of PP1 (NIPP1), an event dependent upon decreased basal cAMP/PKA-dependent signaling. Using a dominant negative NIPP1 construct, we provide evidence that NIPP1 plays a major role in the regulation of both CREB protein expression and CREB-dependent transcription in hypoxia. Furthermore, we demonstrate functional sequellae of such events including altered gene expression and recovery of cellular ATP levels. In summary, we demonstrate that interaction with NIPP1 mediates decreased PP1, activity in hypoxia, an event which may constitute an inherent part of the cellular oxygen-sensing machinery and may play a role in physiologic adaptation to hypoxia. J. Cell. Physiol. 209: 211,218, 2006. © 2006 Wiley-Liss, Inc. [source]

Abnormal expression of PPAR gamma isoforms in the subcutaneous adipose tissue of patients with Cushing's disease

CLINICAL ENDOCRINOLOGY, Issue 1 2007
Fausto Bogazzi
Summary Background, Obesity is a clinical feature of patients with Cushing's disease. Peroxisome proliferators-activated receptor (PPAR), is the master regulator of adipogenesis; however, the expression of PPAR, isoforms in the subcutaneous adipose tissue (SAT) of patients with Cushing's disease is unknown. Aim and methods, The expression of PPAR,1 and PPAR,2 was evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence (PPAR,2 only) in SAT samples of 7 patients with untreated active Cushing's disease (CushingUNTR), 8 with Cushing's disease in remission (CushingREM) after pituitary adenomectomy, 15 normal lean subjects (ControlLEAN), and 15 obese patients (ControlOBE). Results, ControlLEAN had a higher degree of PPAR,1 than PPAR,2 (PPAR,2/PPAR,1 ratio, 0·55 ± 0·35). PPAR,2/PPAR,1 ratio decreased in CushingUNTR (0·10 ± 0·043, P < 0·03 vs. ControlLEAN and ControlOBE), because of either increased PPAR,1 or reduced PPAR,2 expression. PPAR,2/PPAR,1 ratio was 0·48 ± 0·07 in CushingREM patients (P < 0·04 vs. CushingUNTR, P < 0·03 vs. ControlOBE). PPAR,2/PPAR,1 ratio was higher in ControlOBE 0·90 ± 0·38 than in ControlLEAN (P < 0·005 vs. ControlLEAN, P < 0·03 vs. CushingREM, P < 0·009 vs. CushingUNTR). PPAR,2/PPAR,1 ratio was related to serum cortisol levels only in patients with Cushing'disease (r = 0·688, P < 0·02). Conclusions, CushingUNTR patients had an abnormal expression of PPAR, isoforms in SAT related to serum cortisol levels. Although further studies are necessary, it is conceivable that variations in the expression of PPAR, isoforms might have a role in the abnormal adipogenesis of patients with Cushing's disease. [source]