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)

Calpain is a Ca(2+)-regulated cytosolic cysteine protease that exists mainly in two isoforms and mediates crucial cellular functions, including rearrangement of cytoskeletal proteins, transport of the glucose transporter GLUT4, and protein cleavage to activate various receptors and pro-enzymes. Unintentional activation or functional loss of intracellular calpain has been implicated in several pathologies, including neurodegenerative diseases, traumatic brain and spinal cord injuries, cataracts and ischemia-associated injuries. Furthermore, polymorphism in the gene encoding calpain-10 has been associated with increased risk of type 2 diabetes. Recent studies have revealed a novel role for calpain in the progression of toxicant-induced liver damage. Evidence suggests that calpain leaking out of necrotic hepatocytes is highly activated in the extracellular milieu and hydrolyzes proteins in the plasma membrane of neighboring cells leading to progression of injury. Experimental intervention with calpain inhibitors substantially mitigates progression of liver injury initiated by toxicants, thereby preventing acute liver failure, and toxicant-induced animal death, pointing to a new potential therapeutic strategy against acute toxicities.
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PMID:Calpain: a death protein that mediates progression of liver injury. 1586 Mar 69

Altered pain appreciation and autonomic function are hallmarks of Cardiac syndrome X, Irritable bowel syndrome and Reflex sympathetic dystrophy. Both pain appreciation and autonomic function are controlled by the lateral medulla. This hypothesis proposes that lateral medullary ischaemia at a microvascular level is responsible for these syndromes and could also be linked to other conditions where autonomic dysfunction is a major feature such as late-onset asthma, type 2 diabetes and essential hypertension. Autonomic function is controlled by the nucleus tractus solitarius, which acts as the main viscero-afferent nucleus in the brain stem regulating vagal tone. It is particularly susceptible to ischaemia since it is highly metabolically active and lies in a medullary arterial watershed zone. The anatomical route of the vertebral artery through cervical vertebra makes it vulnerable to injury from whiplash with or without any genetic predisposition to atheroma formation. This could make microvascular occlusion commonplace and a plausible explanation for the above syndromes. Ischaemia rather than infarction occurs because of the excellent collateral blood supply in the brainstem. In support of this hypothesis, a new Transcranial doppler ultrasonography arterial signal has been described called small vessel knock, the ultrasound signal of small vessel occlusion. Recent evidence has shown that ultrasound targeting of this signal in the vertebral artery improves clinical symptoms in these syndromes which supports this hypothesis. Two such cases are discussed.
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PMID:Are cardiac syndrome X, irritable bowel syndrome and reflex sympathetic dystrophy examples of lateral medullary ischaemic syndromes? 1589 31

Diabetic neuropathy is a debilitating disorder that occurs in nearly 50 percent of patients with diabetes. It is a late finding in type 1 diabetes but can be an early finding in type 2 diabetes. The primary types of diabetic neuropathy are sensorimotor and autonomic. Patients may present with only one type of diabetic neuropathy or may develop combinations of neuropathies (e.g., distal symmetric polyneuropathy and autonomic neuropathy). Distal symmetric polyneuropathy is the most common form of diabetic neuropathy. Diabetic neuropathy also can cause motor deficits, silent cardiac ischemia, orthostatic hypotension, vasomotor instability, hyperhidrosis, gastroparesis, bladder dysfunction, and sexual dysfunction. Strict glycemic control and good daily foot care are key to preventing complications of diabetic neuropathy.
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PMID:Evaluation and prevention of diabetic neuropathy. 1595 41

Microsurgical techniques increased the operability of patients with critical limb ischemia to more than 95%. However, the percentage of ischemic limb salvage remains limited, especially in diabetic patients with associated tissue gangrene and neuropathy. The study presents a 67 years old female patient with type II diabetes mellitus and critical limb ischemia, complicated with progressive gangrene of the pre-calcaneal region and thus representing a classical indication for thigh amputation. A sequential femur-popliteal-tibial anterior by-pass was performed, followed by soft tissue reconstruction using a latissimus-dorsi musculo-cutaneous free flap. Two years postoperatively, the patient developed clinical signs of symmetrical peripheral distal neuropathy, managed by bilateral posterior tibial nerve decompression. The patient follow-up was of 3 years. Through the entire period, distal pulse (ram of posterior tibial artery) remained present with a good integration of the flap and with absent clinical and paraclinical signs of neuropathy. The patient regained full ambulation. Morphologically and functionally the affected limb is entirely salvaged. Using microsurgical techniques, a more complex and complete approach of the diabetic patient with ischemic-neuropathic syndrome can be considered. This includes revascularization, soft tissue reconstruction and nerve decompression. In selected patients with indication of major amputation these methods offer a salvage option, with excellent long-term results.
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PMID:[Complex microsurgical reconstruction of diabetic foot]. 1595 62

Streptozotocin administration in newborn rats (nSTZ-rats) leads to adults with mild insulin deficiency and normoglycemia, and is accepted as a model of type 2 diabetes. We examined possible differences in the production of inflammatory mediators between healthy and nSTZ-rats after ischemia-reperfusion (I-R). Two-month-old control and nSTZ-rats were randomly separated into control and intestinal I-R groups. After reperfusion, samples were obtained from the portal vein (PV) infrahepatic cava vein (ICV), suprahepatic cava vein (SCV), jejunal wall, and pancreas. Nitric oxide (NO), lipid hydroperoxides (LPO), tumor necrosis factor alpha (TNF-alpha), 60 kDa receptor (sTNF-R1), 80 kDa (sTNF-R2), and intercellular adhesion molecule-1 (ICAM-1), were determined. After I-R, nSTZ-rats showed increased plasma concentrations of LPO, NO, ICAM-1 (0.5141 +/- 0.083 vs 0.024 +/- 0.003, ICV; 0.574 +/- 0.075 vs 0.023 +/- 0.003, SCV; 0.528 +/- 0.067 vs 0.027 +/- 0.003 PV; ng/ml), TNF-alpha (42.4 +/- 5.7 ICV, 248.4 +/- 28.2 SCV, and 33.6 +/- 4.0 PV. In n STZ-rats, vs 4.36 +/- 0.57, 4.74 +/- 0.77, and 3.16 +/- 0.32, respectively, in control rats; pg/ml), and sTNF-R1. Both TNF-alpha and NO plasma levels were higher in SCV than in ICV and PV after I-R. In addition, after I-R, jejunal wall of nSTZ-rats showed an increase of TNF-alpha IL-1, and IL-10 levels. A pre-existing state of glucose intolerance intensifies the inflammatory response after intestinal I-R.
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PMID:Glucose intolerance modifies the inflammatory response after intestinal ischemia-reperfusion. 1608 24

Carotid bodies are monitors of oxygen and glucose delivery to the brain. Faced with the threat of hypoxia or hypoglycemia carotid bodies initiate responses to counter the threat. General corrective action is to improve the perfusion by increasing the arterial blood pressure. Specific corrective actions are to stimulate ventilation to improve oxygen availability or to induce insulin resistance to raise blood glucose levels. Inappropriateness of response caused by misreading of hypoxia as hypoglycemia and hypoglycemia as hypoxia is observed experimentally and clinically. The response to all four types of hypoxia, namely, hypoxic, anemic, histotoxic and ischemic (or stagnant) hypoxia, is stimulation of ventilation and elevation of blood pressure. Ischemia produced by narrowing of the artery to the carotid body activates the carotid bodies. The activation produces hypertension, stimulation of ventilation and insulin resistance that manifests as non-insulin dependent diabetes mellitus. There is epidemiologic and necropsy evidence for the onset of atherosclerotic changes in childhood. Early atherosclerotic changes occurring in the region of carotid arteries and their bifurcation narrows the lumen of the arteries to the carotid bodies and produce hypo-perfusion of the carotid bodies. This ischemic hypoxia is a causative, or at least a permissive factor for hypertension and/or non-insulin dependent diabetes mellitus. It is suggested that neither non-insulin dependent diabetes mellitus causes hypertension nor hypertension causes diabetes mellitus, but both are caused by dysfunctional carotid bodies.
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PMID:Carotid body dysfunction: the possible etiology of non-insulin dependent diabetes mellitus and essential hypertension. 1612 67

Diabetic retinopathy is a frequently observed complication in both type 1 and type 2 diabetes, specially in patients with long term disease and poor glicemic control. Irreversible visual loss appears at the final stages of diabetic retinopathy and it is considered one of the most tragic of diabetic complications. It is also considered an important factor of morbidity and has a high economical impact once it is the leading cause of blindness. The pathophysiology of the retinal microvascular alterations is related to the chronic hyperglycemia that leads to the following circulatory disturbances: loss of vascular tonus, increase in vascular permeability, edema and exudation, with vascular obstruction and ischemia that stimulates neovascularization, which may lead to fibrous retraction and vitreous hemorrhages with retinal detachment. Recent studies have indicated that the strict glicemic and blood pressure controls are effective in reducing or blocking the progression of retinopathy. Up to now no pharmacological agents have shown to be effective in preventing or reducing neovascularization and visual loss. Presently, the most effective available treatment for proliferative retinopathy is laser photocoagulation. Further studies are needed to obtain new products and technologies that could effectively prevent or block retinopathy progression.
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PMID:[Diabetic retinopathy]. 1618 49

An episode of acute heart failure syndromes (AHFS) can be defined as a rapid or gradual onset of signs and symptoms of heart failure (HF) in hospital admission and can arise from a variety of pathophysiologic mechanisms. This article reviews our current understanding of the pathophysiology of AHFS in order to identify potential therapeutic targets. Most patients with AHFS present with either normal systolic blood pressure or elevated blood pressure. Patients who present with elevated systolic blood pressure usually have pulmonary congestion and a relatively preserved left ventricular ejection fraction (LVEF), and have symptoms that typically develop abruptly, these patients often are elderly women. Patients with normal systolic blood pressure presenting with systemic congestion and reduced LVEF are usually younger, with a history of chronic HF, and have symptoms that develop gradually over days or weeks. Accordingly, most episodes of AHFS can be classified as either "vascular" failure or "cardiac" failure. In addition to the abnormal hemodynamics (increase in pulmonary capillary wedge pressure and/or decrease in cardiac output) that characterize patients with AHFS, myocardial injury--which may be related to a decrease in coronary perfusion and/or further activation of neurohormones and renal dysfunction (ie, the cardiorenal syndrome)--probably contributes to short-term and post-discharge cardiac events. Patients with AHFS also have significant cardiac and non-cardiac underlying conditions that contribute to the pathogenesis of AHFS, including coronary artery disease (ischemia, hibernating myocardium, and endothelial dysfunction), hypertension, atrial fibrillation, and type 2 diabetes mellitus. The goals of therapy for AHFS should be not only to improve symptoms and hemodynamics, but also to preserve or improve renal function and prevent myocardial damage.
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PMID:Pathophysiologic targets in the early phase of acute heart failure syndromes. 1619 54

Recently, type 2 diabetes seems to be increasing annually in all developed countries. The outcome of type 2 diabetes is often tragic due to succession of complications including renal disorders requiring hemodialysis, blindness, and limb amputation. The expenses for the care of diabetic patients are also a large burden on the society. These circumstances strongly indicate the necessity of prevention. For satisfactory prevention, the clarification of the etiology related to lifestyle is important, but it remains insufficient to date. In this paper, we present a hypothesis of the etiology of type 2 diabetes from the viewpoint of microcirculation. As mentioned later, an unhealthy lifestyle first causes disturbance of the microcirculation, and a portion of the blood is considered to bypass the capillaries via arteriovenous shunts. This prevents the delivery of glucose and insulin to cells of peripheral tissues, causing hyperglycemia unrelated to the cell insulin sensitivity or the endocrine state, i.e., apparent reduction of insulin sensitivity. Disturbance of the microcirculation also causes oxidative stress in peripheral tissues by inducing ischemia and hypoxia. This oxidative stress is considered to further exacerbate reduction of insulin sensitivity. This hypothesis is supported by the well-known fact that insulin sensitivity recovers with improvement in lifestyle including moderate exercise.
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PMID:Disturbance of microcirculation due to unhealthy lifestyle: Cause of type 2 diabetes. 1624 54

Diabetes, with hyperglycemia as its hallmark, is a major risk factor for ischemic heart disease. The role of coronary disease in the adverse prognosis of diabetes is controversial although the higher prevalence and extension of coronary atherosclerosis is well recognized. The paper reviews the available evidence of coronary involvement in diabetes with particular emphases on microcirculation. Several studies, mainly in type 2 diabetes, have documented a reduced coronary flow reserve even in absence of coronary obstructive disease and using different techniques. Microcirculatory dysfunction affects the left ventricle globally as well as regionally. However, neither the prevalence of such abnormality in the diabetic population nor its time course and its prognostic value have been investigated in specifically addressed studies. In fact, a relatively large number of studies on myocardial perfusion performed by single-photon myocardial scintigraphy in asymptomatic diabetics rather address the problem of the prevalence of silent ischemia and its prognostic value. In spite of such limitation it can be speculated from the few available studies with known coronary anatomy that the prevalence of exclusively regional disturbances of perfusion (scintigraphic defects) in absence of obstructive coronary disease is not marginal as it ranges from 11 to 63%. Extensive research is still required to define the pathogenesis and the actual clinical relevance of coronary microcirculatory dysfunction in diabetes.
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PMID:Large and micro coronary vascular involvement in diabetes. 1641 82


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