Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelin-1 (ET-1) was first characterized as a potent vasoconstrictor and is overexpressed in the vasculature in different models of hypertension, such as deoxycorticosterone acetate-salt rats, Dahl salt-sensitive rats, and stroke-prone spontaneously hypertensive rats. Moreover, patients with moderate to severe hypertension present increased vascular levels of prepro-ET-1 mRNA. In addition to their blood pressure-lowering effects, ET receptor antagonists are able to reduce vascular growth. Recent data suggest the involvement of an inflammatory response in the effects of ET-1, which contributes to vascular remodeling and endothelial dysfunction. Increasing evidence underscores the potential therapeutic benefit of ET receptor antagonists in different hypertension-related complications, not only in essential hypertension, but also in patients with type 2 diabetes.
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PMID:Role of endothelin-1 in hypertension. 1264 14

Although a salted diet appears to be a sine qua non for the development of essential hypertension, low-salt diets often have a modest or even negligible impact on the blood pressure of hypertensives; this suggests that salt, perhaps often acting in concert with other aspects of a modern, rich diet, may set in place certain metabolic vicious cycles that sustain blood pressure elevation even when dietary salt is eliminated. Therapeutic fasting is known to lower elevated blood pressure - presumably in large part because it minimizes insulin secretion - and may have the potential to break some of these vicious cycles. Goldhamer has recently reported that a regimen comprised of a water-only fast of moderate duration, followed by a transition to a low-fat, low-salt, whole-food vegan diet, achieves dramatic reductions in the blood pressure of hypertensives, such that the large majority of patients can be restored to normotensive status, in the absence of any drug therapy. Although long-term follow-up of these subjects has been sporadic, the available data suggest that these large reductions is blood pressure can be conserved in patients who remain compliant with the follow-up diet - in other words, a 'cure' for hypertension may be feasible. If a protein-sparing modified fast can be shown to be virtually as effective as a total fast for achieving these benefits, it may be possible to implement this regimen safely on an outpatient basis. The ability of therapeutic fasts to break metabolic vicious cycles may also contribute to the efficacy of fasting in the treatment of type 2 diabetes and autoimmune disorders. As a general principle, if a metabolic disorder is susceptible to prevention - but not reversal - by a specific diet, and therapeutic fasting has a temporary favorable impact on this disorder, then a more definitive therapy may consist of a therapeutic fast, followed up by the protective diet as a maintenance regimen.
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PMID:A preliminary fast may potentiate response to a subsequent low-salt, low-fat vegan diet in the management of hypertension - fasting as a strategy for breaking metabolic vicious cycles. 1271 Aug 93

The salt-inducible kinases (SIKs) are a family of related serine-threonine kinases. In cultured adrenocortical cells, SIK1 is rapidly but transiently induced by adrenocorticotropin (ACTH) treatment, suggesting that it contributes to ACTH-mediated induction of steroidogenic enzymes. However, ACTH treatment of Y1 mouse adrenocortical cells stimulates a rapid translocation of SIK1 from the nucleus to the cytoplasm, and SIK1 represses the transcription of a steroidogenic enzyme by inhibiting the action of cAMP-responsive elements in the promoter. These studies suggest that SIK1 has a role in the fine tuning of steroidogenic enzyme production during the initial phase of steroidogenesis. SIK2 is found in adipocytes and phosphorylates a specific serine residue in insulin receptor substrate-1. This finding, along with the fact that its expression is raised in the white adipose tissue of mice with type 2 diabetes mellitus, suggests that SIK2 might be involved in metabolic regulation in adipose tissue. Thus, members of the SIK family are emerging as important modulators of key processes such as steroid hormone biosynthesis by the adrenal cortex and insulin signaling in adipocytes.
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PMID:Salt-inducible kinase in steroidogenesis and adipogenesis. 1469 22

Glitazones are used in the treatment of type 2 diabetes as efficient insulin sensitizers. They can, however, induce peripheral edema through an unknown mechanism in up to 18% of cases. In this double-blind, randomized, placebo-controlled, four-way, cross-over study, we examined the effects of a 6-wk administration of pioglitazone (45 mg daily) or placebo on the blood pressure, hormonal, and renal hemodynamic and tubular responses to a low (LS) and a high (HS) sodium diet in healthy volunteers. Pioglitazone had no effect on the systemic and renal hemodynamic responses to salt, except for an increase in daytime heart rate. Urinary sodium excretion and lithium clearance were lower with pioglitazone, particularly with the LS diet (P < 0.05), suggesting increased sodium reabsorption at the proximal tubule. Pioglitazone significantly increased plasma renin activity with the LS (P = 0.02) and HS (P = 0.03) diets. Similar trends were observed with aldosterone. Atrial natriuretic levels did not change with pioglitazone. Body weight increased with pioglitazone in most subjects. Pioglitazone stimulates plasma renin activity and favors sodium retention and weight gain in healthy volunteers. These effects could contribute to the development of edema in some subjects treated with glitazones.
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PMID:Effects of the peroxisomal proliferator-activated receptor-gamma agonist pioglitazone on renal and hormonal responses to salt in healthy men. 1500 99

Hypertension frequently coexists with diabetes mellitus, occurring twice as frequently in diabetic as in nondiabetic persons. It accounts for up to 75% of added cardiovascular disease (CVD) risk in people with diabetes, contributing significantly to the overall morbidity and mortality in this high-risk population. Patients with hypertension are two times more prone to have diabetes than are normotensive persons. Hypertension substantially increases the risk for coronary heart disease (CHD), stroke, retinopathy, and nephropathy. In patients with type 2 diabetes, hypertension usually clusters with the other components of the cardiometabolic syndrome, such as microalbuminuria, central obesity, insulin resistance, dyslipidemia, hypercoagulation, increased inflammation, and left ventricular hypertrophy (LVH). In type 1 diabetes, hypertension often occurs subsequent to the development of diabetic nephropathy. Hypertension in people with diabetes is characterized by volume expansion, increased salt sensitivity, isolated systolic blood pressure (BP) elevation, loss of the nocturnal dipping of BP and pulse, and increased propensity toward orthostatic hypotension and albuminuria. Among the treatment strategies tested in hypertensive diabetic persons, low-density lipoprotein (LDL)-cholesterol lowering to less than 100 mg/dL and aggressive BP control to less than 130/80 mm Hg have proven effective in CVD risk reduction. The combination of two or more drugs is usually necessary to achieve the target BP.
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PMID:Diabetes, hypertension, and cardiovascular derangements: pathophysiology and management. 1512 75

Effects of magnesium (Mg) supplementation on nine mild type 2 diabetic patients with stable glycemic control were investigated. Water from a salt lake with a high natural Mg content (7.1%) (MAG21) was used for supplementation after dilution with distilled water to 100mg/100mL; 300mL/day was given for 30 days. Fasting serum immunoreactive insulin level decreased significantly, as did HOMA squareR (both p < 0.05). There was also a marked decrease of the mean triglyceride level after supplementation. The patients with hypertension showed significant reduction of systolic (p < 0.01), diastolic (p = 0.0038), and mean (p < 0.01) blood pressure. The salt lake water supplement, MAG21, exerted clinical benefit as a Mg supplement in patients with mild type 2 diabetes mellitus.
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PMID:Clinical efficacy of magnesium supplementation in patients with type 2 diabetes. 1546 52

A novel series of beta-amino amides incorporating fused heterocycles, i.e., triazolopiperazines, were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-IV) for the treatment of type 2 diabetes. (2R)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine (1) is a potent, orally active DPP-IV inhibitor (IC(50) = 18 nM) with excellent selectivity over other proline-selective peptidases, oral bioavailability in preclinical species, and in vivo efficacy in animal models. MK-0431, the phosphate salt of compound 1, was selected for development as a potential new treatment for type 2 diabetes.
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PMID:(2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine: a potent, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. 1563 8

Several experimental and clinical evidences have linked an enhanced production of reactive oxygen species (ROS) to certain diseases of the cardiovascular system including hypertension and diabetes. However, it has never been clearly established whether the enhanced oxidative stress observed in those conditions is primary or secondary to the pathological process. Our experimental studies have permitted to demonstrate that ROS, mainly through the production of superoxide anion, can cause important alterations in the cellular signal transduction systems characterized by an enhanced production of inositol triphosphate and a reduced production of cyclic GMP in cultured vascular smooth muscle cells (SMC), thus favouring the vasoconstriction. Since those effects were found to be increased in SMC from spontaneously hypertensive rats (SHR), this suggested a greater sensitivity of the vascular tissue of SHR to the oxidative stress. Moreover, we also have observed an increased production of superoxide anion in the aorta of rats made hypertensive according to the SHR, glucose or angiotensin-induced and DOCA-salt models during the development of hypertension. Since the superoxide anion production could be correlated with the level of blood pressure and since the development of hypertension could be either totally prevented or markedly attenuated by chronic treatment with potent antioxidative therapies such as alpha lipoic acid or aspirin, this suggested a major contribution of vascular superoxide anion production in the development of hypertension in those models. Moreover, the development of insulin resistance, which is associated to the model of glucose-induced hypertension, was also found to be prevented by chronic antioxidant therapies, thus suggesting that oxidative stress plays an important role as well in the development of insulin resistance and type 2 diabetes. In conclusion, it appears that oxidative stress may constitute a major pathogenic factor in the development of hypertension and type 2 diabetes. Moreover, our studies suggest that the chronic treatment with appropriate antioxidative therapies could prevent the development of hypertension and diabetes as well as their complications in various experimental models of hypertension.
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PMID:Oxidative stress in hypertension. 1570 13

The inhibition of protein-tyrosine phosphatase 1B (PTP1B) is a potential target for treatment of type 2 diabetes. Vanadium and zinc metal coordinated complexes have insulin-enhancing activities, and while vanadium compounds inhibit PTP1B, little is known on the mode of action of zinc compounds. In this study we developed an automated PTP1B inhibition assay that allows for a rapid assessment of the PTP1B inhibition strength of candidate compounds. Synthetic vanadium(IV) and zinc(II) complexes were evaluated: IC50 values for vanadium complexes ranged from 0.06 to 0.8 microM whereas for zinc compounds, values were above 10 microM. Vanadium sulfate, a non-conjugated inorganic salt, had stronger inhibition activity than any of the conjugated metal complexes.
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PMID:Development of an automated protein-tyrosine phosphatase 1B inhibition assay and the screening of putative insulin-enhancing vanadium(IV) and zinc(II) complexes. 1574 40

Our hunter-gatherer ancestors appeared to survive on little salt. When today's rural dwellers move to urban environments, they increase their salt intake and the salt-sensitive among them become prone to age-related increase in blood pressure and hypertension. This paper reviews our knowledge of the mechanisms of salt disposal and plasma volume regulation, salt consumption in human evolution, salt intake and prevalence of hypertension, and the results of interventions aimed at modulating both. Finally, it discusses current hypotheses on the mechanisms of selective pressure that may have favored the emergence of a salt-sensitive, hypertensive genotype. Similar to 'thrifty' genes, which supported energy savers in times of scarcity, but may now be causing obesity and type 2 diabetes, 'thirsty' genes, by acting on salt and water retention, might have helped individuals survive the challenge of volume-depleting illnesses, especially when combined with stress-inducing situations, but may now cause high BP and related damage in the post-reproductive age.
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PMID:Salt and hypertension: a phylogenetic perspective. 1575 81


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