1- ??? ?????? ????? ?????Diabetes - Type 1 Insulin-dependent diabetes mellitus; (???? ???????) Juvenile onset ? ????? ????? ????? ?????? ???? ?? ????????? ???? ???? ????????? (????? ????????? ?????? ?? ???? ) ?????? ????? ????? Auto-Antibodies ?? ?? ??????, ? ????? ????? ??? ??????? ????????? ??? ???? ? ?? ???? ??????? ?????? ???? KetoAcidosis .
2- ??? ?????? ????? ?????? Type 2 Diabetes- MellitusNoninsulin-dependent diabetes mellitus ????? ????? ?????? ????????? ?? ??? ??????? ??? ?? ?????? ??.
3- ????? ????? ?????? ??? ??????? ?????? Cushing's Syndrome , ??? ????? ????? ??????? Hyperthyroidism ? ????? ???????? (???????) Acromegaly . 4- ????? ??? ???????? ??? ????? ????? ??????? Thyroid Hormone ? ??? ??????????? Nicotinic Acid ? ???????????? Steroids . 5- ????? ?????????? ????????? ???? ???? ??? ????????? ??? ?????? ????? ??????????? Cytomegalo Virus ? ?????? ???????? Congenital Rubella (?? ??? ??? ?????? ??????? ?? ???? ????? ?????). 1- ?? ??????? ?????? ??? ????? ????? ?? ???? ???? ?? ??? ??????? ??????? ??????? ? ????? ? ??????? ?????? ????? 50 - 75 % . 4- ?? ???????? ?????? ????? ???? ????? ?? ?????? ??????? , ? ??????? ???????? ?????? ?? ??? ????? ??????? ??? ????? ?? ???? ? ???? ?? ?????????. The transcriptional activity of TRs is modulated by multiple factors including various TR isoforms, diverse thyroid hormone response elements, different heterodimeric partners, coregulators, and the cellular location of TRs. Thyroid hormone mimetics increase HDL synthesis, HDL reuptake, LDL uptake, the conversion of cholesterol to bile acid, and decrease fatty acid synthesis by mediating the expression of apolipoprotein A1 (APOA1), scavenger receptor B1 (SRB1), LDL receptor (LDLR), cytochrome P450 7A (CYP7A), and sterol response element binding protein (SREBP1) as indicated, respectively. Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Mice with a targeted mutation in the thyroid hormone beta receptor gene exhibit impaired growth and resistance to thyroid hormone. Increased sensitivity to thyroid hormone in mice with complete deficiency of thyroid hormone receptor alpha. Retardation of post-natal development caused by a negatively acting thyroid hormone receptor alpha1.
A 43-kDa protein related to c-Erb A alpha 1 is located in the mitochondrial matrix of rat liver. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Identification of liver X receptor-retinoid X receptor as an activator of the sterol regulatory element-binding protein 1c gene promoter. In the present review, we summarize recent advance in understanding the molecular mechanisms of thyroid hormone action obtained from human subject research, thyroid hormone mimetics application, TR isoform-specific knock-in mouse models, and mitochondrion study with highlights in metabolic regulations. Chicken thyroid hormone receptor alpha requires the N-terminal amino acids for exclusive nuclear localization. Thyroid hormone receptor beta mutants: Dominant negative regulators of peroxisome proliferator-activated receptor gamma action. Distinct dysregulation of lipid metabolism by unliganded thyroid hormone receptor isoforms. 3,5,3a€?-Triiodothyronine actively stimulates UCP in brown fat under minimal sympathetic activity. A variant form of the nuclear triiodothyronine receptor c-ErbAalpha1 plays a direct role in regulation of mitochondrial RNA synthesis. Hypothyroidism in rats decreases peripheral glucose utilisation, a defect partially corrected by central leptin infusion.

Multiple mechanisms for regulation of the transcriptional activity of thyroid hormone receptors.
Thyroid hormone exerts negative feedback on hypothalamic type 4 melanocortin receptor expression. DNA wrapping and bending by a mitochondrial high mobility group-like transcriptional activator protein.
Half-site spacing and orientation determines whether thyroid hormone and retinoic acid receptors and related factors bind to DNA response elements as monomers, homodimers, or heterodimers. Novel functions of thyroid hormone receptor mutants: beyond nucleus-initiated transcription.
Stoichiometry of mitochondrial transcripts and regulation of gene expression by mitochondrial transcription factor A.
Thyroid hormone receptor beta (TRbeta) and liver X receptor (LXR) regulate carbohydrate-response element-binding protein (ChREBP) expression in a tissue-selective manner. Lack of thyroid hormone receptor alpha1 is associated with selective alterations in behavior and hippocampal circuits.
Carbohydrate response element binding protein gene expression is positively regulated by thyroid hormone. Differential and tissue-specific regulation of the multiple rat c-erbA messenger RNA species by thyroid hormone. Regional differences in intramyocellular lipids in humans observed by in vivo 1H-MR spectroscopic imaging. Brain glucose utilization in mice with a targeted mutation in the thyroid hormone alpha or beta receptor gene. Thyroid hormone receptor alpha isoforms generated by alternative splicing differentially activate myosin HC gene transcription.
Thyroid hormone regulates carnitine palmitoyltransferase Ialpha gene expression through elements in the promoter and first intron. A targeted dominant negative mutation of the thyroid hormone alpha 1 receptor causes increased mortality, infertility, and dwarfism in mice. The selenoenzyme family of deiodinase isozymes controls local thyroid hormone availability. Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study. A thyroid hormone receptor alpha gene mutation (P398H) is associated with visceral adiposity and impaired catecholamine-stimulated lipolysis in mice. Temperature homeostasis in transgenic mice lacking thyroid hormone receptor-alpha gene products. Modulation of thyroid hormone action by mutant thyroid hormone receptors, c-erbA alpha 2 and peroxisome proliferator-activated receptor: evidence for different mechanisms of inhibition.
Alternative splicing generates messages encoding rat c-erbA proteins that do not bind thyroid hormone. Cytosolic action of thyroid hormone leads to induction of hypoxia-inducible factor-1alpha and glycolytic genes. Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histone deacetylase.

Functional relationship of thyroid hormone-induced lipogenesis, lipolysis, and thermogenesis in the rat. Characterization of seven novel mutations of the c-erbA beta gene in unrelated kindreds with generalized thyroid hormone resistance.
Triiodothyronine treatment increases substrate cycling between pyruvate carboxylase and malic enzyme in perfused rat liver. Substrate cycling between pyruvate and oxaloacetate in awake normal and 3,3a€?-5-triiodo-L-thyronine-treated rats. Study of glucose and lipid metabolism by continuous indirect calorimetry in Gravesa€™ disease: effect of an oral glucose load. Expression of uncoupling protein 1 in mouse brown adipose tissue is thyroid hormone receptor-beta isoform specific and required for adaptive thermogenesis.
Thyroid hormonea€”sympathetic interaction and adaptive thermogenesis are thyroid hormone receptor isoforma€”specific. Thyroid function is associated with components of the metabolic syndrome in euthyroid subjects. PPARalpha and PPARgamma activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene.
Vitamin D3-thyroid hormone receptor heterodimer polarity directs ligand sensitivity of transactivation. Assessment of skeletal muscle triglyceride content by (1)H nuclear magnetic resonance spectroscopy in lean and obese adolescents: relationships to insulin sensitivity, total body fat, and central adiposity. Hypermetabolism in mice caused by the central action of an unliganded thyroid hormone receptor alpha1. Tissue-specific stabilization of the thyroid hormone beta1 nuclear receptor by phosphorylation. Anxiety, memory impairment, and locomotor dysfunction caused by a mutant thyroid hormone receptor alpha1 can be ameliorated by T3 treatment. Behavioral inhibition and impaired spatial learning and memory in hypothyroid mice lacking thyroid hormone receptor alpha.
Isoform-specific thyroid hormone receptor antibodies detect multiple thyroid hormone receptors in rat and human pituitaries. Differential sensitivity of thyroid hormone receptor isoform homodimers and mutant heterodimers to hormone-induced dissociation from deoxyribonucleic acid: its role in dominant negative action. Finally, as future perspectives, we share our thoughts about current challenges and possible approaches to promote our knowledge of thyroid hormone action in metabolism. Alpha and beta thyroid hormone receptor (TR) gene expression during auditory neurogenesis: evidence for TR isoform-specific transcriptional regulation in vivo. Glucose-turnover values and futile-cycle activities obtained with 14C- and 3H-labelled glucose. Beta 1- and beta 2-adrenergic receptors and cyclic adenosine 3a€?,5a€?-monophosphate generation.

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