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)

The number of mammalian calpain protease family members has grown to 14 on last count. Overactivation of calpain 1 and calpain 2 (and their small subunit) has long been tied to acute neurological disorders (e.g. stroke and traumatic brain injury) and recently to Alzheimer's disease. Loss-of-function mutations of the calpain 3 gene have now been identified as the cause of limb-girdle muscular dystrophy 2A. Calpain 10 was recently identified as a susceptibility gene for type 2 diabetes, whereas calpain 9 appears to be a gastric cancer suppressor. This review describes our current understanding of the calpain family members and their mechanistic linkages to the aforementioned diseases as well as other emerging pathological conditions.
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PMID:The calpain family and human disease. 1151 96

Calpain, a Ca(2+)-requiring cytoplasmic cysteine protease, plays indispensable roles in various cellular functions such as signal transduction, cell growth and differentiation, apoptosis, necrosis, and so on. Although most of the detailed physiological functions of calpains have not yet been elucidated, the importance of calpain is obvious from the increasing numbers of papers describing relationships between human disease states (such as Alzheimer's disease, cataract, and muscular dystrophies) and malfunction of calpain. One of the recent remarkable topics of calpain is that a single nucleotide polymorphism of CAPN10, the gene for calpain 10, is related to type 2 diabetes. However, physiological functions of calpain 10 and its relation to diabetes are still unclear. Among 14 human calpain genes, mutations in CAPN3, the gene for p94/calpain 3a and Lp82/calpain 3b, are the only example that genetically connects the calpain gene and human disease, in this case, limb-girdle muscular dystrophy type 2A (LGMD2A). p94 has unique characteristics such as apparent Ca(2+)-independent activation and very rapid autolytic activity, which are dependent on p94-specific regions, NS, IS1, and IS2. Based on the 3D structures of micro - and m-calpain, molecular functions of p94 in relation to LGMD2A are discussed, with the hope of providing us with some clues to understand calpain functions and its relationships to human diseases.
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PMID:[Calpain and pathology in view of structure-function relationships]. 1284 69

Type 2 diabetes mellitus (T2DM) can lead to death without treatment and it has been predicted that the condition will affect 215 million people worldwide by 2010. T2DM is a multifactorial disorder whose precise genetic causes and biochemical defects have not been fully elucidated, but at both levels, calpains appear to play a role. Positional cloning studies mapped T2DM susceptibility to CAPN10, the gene encoding the intracellular cysteine protease, calpain 10. Further studies have shown a number of noncoding polymorphisms in CAPN10 to be functionally associated with T2DM while the identification of coding polymorphisms, suggested that mutant calpain 10 proteins may also contribute to the disease. Here we review recent studies, which in addition to the latter enzyme, have linked calpain 5, calpain 3, and its splice variants, calpain 2 and calpain 1 to T2DM-related metabolic pathways along with T2DM-associated phenotypes, such as obesity and impaired insulin secretion, and T2DM-related complications, such as epithelial dysfunction and diabetic cataract.
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PMID:Calpains and their multiple roles in diabetes mellitus. 1715 22

Calpains, particularly conventional dimeric calpains, have claimed to be involved in the cell degeneration processes that characterize numerous disease conditions linked to dysfunctions of cellular Ca2+ homeostasis. The evidence supporting their involvement has traditionally been indirect and circumstantial, but recent work has added more solid evidence supporting the role of ubiquitous dimeric calpains in the process of neurodegeneration. The only disease condition in which a calpain defect has been conclusively involved concerns an atypical monomeric calpain: the muscle specific calpain-3, also known as p94. Inactivating defects in its gene cause a muscular dystrophy termed LGMD-2A. The molecular mechanism by which the absence of the proteolytic activity of calpain-3 causes the dystrophic process is unknown. Another atypical calpain, which has been characterized recently as a Ca2(+)-dependent protease, calpain 10, appears To be involved in the etiology of type 2 diabetes. The involvement has been inferred essentially from genetic evidence. Also in the case of type 2 diabetes the molecular mechanisms that could link the disease to calpain 10 are unknown.
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PMID:Calpains and human disease. 1819 33

In this study, we compared the clinicopathological findings of two autopsy cases of patients with calpainopathy (LGMD2A) from different families. The patient in case 1 was a 72-year-old man with a history of type 2 diabetes mellitus. He exhibited recent memory impairments from the age of 70. ECG revealed an incomplete right bundle branch block. A homozygous frameshift mutation c.1796dupA was found in the CAPN3 gene. Cause of death was respiratory insufficiency and heart failure. The patient in case 2 was a 70-year-old man with a history of hypertension. ECG revealed an incomplete right bundle branch block. A homozygous missense mutation c.1080G>C (p.Trp360Cys) in CAPN3 gene was identified. Cause of death was ischemic cardiomyopathy and systemic circulatory failure. In both cases, muscle pathology revealed severe dystrophic changes. In case 2, cardiac hypertrophy and old myocardial infarcts with stenosis of coronary arteries were observed. Histological examination of the sinoatrial node showed fatty infiltration with ischemic changes in case 2. In both cases, the patients' brains showed cerebral atrophy and well preserved neurons. Calpain 3 abnormality was correlated with skeletal muscle involvement. It should be considered that LGMD2A might be complicated by dysfunction of the cardiac conduction system.
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PMID:[A clinicopathological investigation of two autopsy cases of calpainopathy (LGMD2A)]. 2520 May 81