Calsequestrin expression and calcium binding is increased in streptozotocin-induced diabetic rat skeletal muscle though not in cardiac muscle

Howarth, FC; Glover, Louise; Culligan, Kevin; Ma, Qiang; Ohlendieck, Kay

doi:10.1007/s00424-002-0784-2

Cited by 15 publications

(12 citation statements)

References 50 publications

(75 reference statements)

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“…Since dystrophin is reduced in diabetic muscle, the ion-regulatory apparatus might also be affected in type 2 diabetes. We could previously show that in a drug-induced animal model of type 1 diabetes the Ca 2+ -binding element calsequestrin is drastically up-regulated, probably compensating for abnormal accumulations of elevated intracellular Ca 2+ levels in diabetic muscle fibres (Howarth et al, 2002). However, screening of diabetic GK muscle samples with a library of monoclonal antibodies to key ion-handling proteins did not detect abnormal expression levels in signalling elements that might be indirectly linked to insulin resistance.…”

Section: Article In Pressmentioning

confidence: 94%

Expression of the skeletal muscle dystrophin–dystroglycan complex and syntrophin-nitric oxide synthase complex is severely affected in the type 2 diabetic Goto–Kakizaki rat

Mulvey

Harno

Keenan

et al. 2005

European Journal of Cell Biology

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The inability of insulin to stimulate glucose metabolism in skeletal muscle fibres is a classic characteristic of type 2 diabetes. Using the non-obese Goto-Kakizaki rat as an established animal model of this type of diabetes, sucrose gradient centrifugation studies were performed and confirmed the abnormal subcellular location of the glucose transporter GLUT4. In addition, this analysis revealed an unexpected drastic reduction in the surface membrane marker b-dystroglycan, a dystrophin-associated glycoprotein. Based on this finding, a comprehensive immunoblotting survey was conducted which showed a dramatic decrease in the Dp427 isoform of dystrophin and the a/b-dystroglycan subcomplex, but not in laminin, sarcoglycans, dystrobrevin, and excitation-contraction-relaxation cycle elements. Thus, the backbone of the trans-sarcolemmal linkage between the extracellular matrix and the actin membrane cytoskeleton might be structurally impaired in diabetic fibres. Immunohistochemical studies revealed that the reduction in the dystrophin-dystroglycan complex does not induce obvious signs of muscle pathology, and is neither universal in all fibres, nor fibre-type specific. Most importantly, the expression of a-syntrophin and the syntrophinassociated neuronal isoform of nitric oxide synthase, nNOS, was demonstrated to be severely reduced in diabetic fibres. The loss of the dystrophin-dystroglycan complex and the syntrophin-nNOS complex in selected fibres suggests a weakening of the sarcolemma, abnormal signalling and probably a decreased cytoprotective mechanism in diabetes. Impaired anchoring of the cortical actin cytoskeleton via dystrophin might interfere with the proper recruitment of the glucose transporter to the surface membrane, following stimulation by insulin or muscle contraction. This may, at least partially, be responsible for the insulin resistance in diabetic skeletal muscles.

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Section: Article In Pressmentioning

confidence: 94%

Expression of the skeletal muscle dystrophin–dystroglycan complex and syntrophin-nitric oxide synthase complex is severely affected in the type 2 diabetic Goto–Kakizaki rat

Mulvey

Harno

Keenan

et al. 2005

European Journal of Cell Biology

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“…CASQ1 binds and releases large quantities of Ca 2ϩ rapidly through its high capacity (40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50) per CASQ molecule) and relatively low-affinity interactions with Ca 2ϩ (28,45). Howarth et al (31) investigated the expression of CASQ and Ca 2ϩ binding in cardiac and skeletal muscle from the streptozotocininduced diabetic rat and found no significant changes in heart but an increase in the relative abundance of CASQ and CASQ-like proteins in skeletal muscle. Together, these data suggest that CASQ1 may play an important role in insulin-and/or contraction-stimulated glucose transport.…”

Section: Discussionmentioning

confidence: 99%

“…Calcium release from the sarcoplasmic reticulum into the cytosol has been shown to regulate GLUT4 expression (29) and glucose transport in muscle (30). Furthermore, Howarth et al (31) reported that CASQ1 expression and calcium binding is increased in streptozotocin-induced diabetic rat skeletal muscle. We hypothesized that variation in CASQ1 may affect insulin action on glucose uptake and glycogen synthesis in skeletal muscle and thus type 2 diabetes susceptibility.…”

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confidence: 99%

Polymorphism in the Calsequestrin 1 (CASQ1) Gene on Chromosome 1q21 Is Associated With Type 2 Diabetes in the Old Order Amish

Damcott

Sabra

et al. 2004

Diabetes

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Calsequestrin (CASQ)1 is involved in intracellular storage and release of calcium, a process that has been shown to mediate glucose transport in muscle. Its gene, CASQ1, is encoded on chromosome 1q21, a region that has been linked to type 2 diabetes in the Amish and several other populations. We screened all 11 exons, exon-intron junctions, and the proximal regulatory region of CASQ1 for mutations. We detected four novel single nucleotide polymorphisms (SNPs) (؊1470C3 T, ؊1456delG, ؊1366insG, and 593C3 T). Ten informative SNPs within CASQ1 were genotyped in Amish subjects with type 2 diabetes (n ‫؍‬ 145), impaired glucose tolerance (n ‫؍‬ 148), and normal glucose tolerance (n ‫؍‬ 358). Rs2275703 and rs617698 in introns 4 and 2 were significantly associated with type 2 diabetes (P ‫؍‬ 0.008 and 0.04, respectively); three other SNPs showed borderline evidence for association to type 2 diabetes (P ‫؍‬ 0.076 -0.093). Furthermore, in nondiabetic subjects (n ‫؍‬ 754), both rs2275703 and rs617698 were significantly associated with glucose area under the curve during an oral glucose tolerance test (P ‫؍‬ 0.035 and 0.013, respectively). Haplotype analysis suggested that no haplotype could explain these associations better than rs2275703. These findings, coupled with similar findings in Utah Caucasians, suggest that sequence variation in CASQ1 may influence risk of type 2 diabetes. Diabetes 53: [3292][3293][3294][3295][3296][3297][3298][3299] 2004

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“…Examples of differentially expressed genes previously associated with obesity and T2D included complement component 1, r component (C1r), calsequestrin (Casq1) and secreted protein, acidic, cysteine-rich protein (Sparc). [25][26][27][28] Additional bioinformatics identified four candidate genes not previously associated with metabolic disease for further study. These genes were sushi domain containing 2 (Susd2, NM_019601), collagen and calcium-binding EGF domains 1 (Ccbe1, NM_133459), periostin (Postn, NM_006475) and decorin (Dcn, NM_133503).…”

Section: Development Of Sst In Conjunction With Microarraymentioning

confidence: 99%

Identification of secreted proteins associated with obesity and type 2 diabetes in Psammomys obesus

et al. 2009

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Objective: Skeletal muscle produces a variety of secreted proteins that have important roles in intercellular communication and affects processes such as glucose homoeostasis. The objective of this study was to develop a novel Signal Sequence Trap (SST) in conjunction with cDNA microarray technology to identify proteins secreted from skeletal muscle of Psammomys obesus that were associated with obesity and type 2 diabetes (T2D). Design: Secreted proteins that were differentially expressed between lean, normal glucose tolerant (NGT), overweight and impaired glucose tolerant (IGT) and obese, T2D P. obesus were isolated using SST in conjunction with cDNA microarray technology. Subsequent gene expression was measured in tissues from P. obesus by real-time PCR (RT-PCR). Results: The SST yielded 1600 positive clones, which were screened for differential expression. A total of 91 (B6%) clones were identified by microarray to be differentially expressed between NGT, IGT and T2D P. obesus. These clones were sequenced to identify 51 genes, of which only 27 were previously known to encode secreted proteins. Three candidate genes not previously associated with obesity or type 2 diabetes, sushi domain containing 2, collagen and calcium-binding EGF domains 1 and periostin (Postn), as well as one gene known to be associated, complement component 1, were shown by RT-PCR to be differentially expressed in skeletal muscle of P. obesus. Further characterization of the secreted protein Postn revealed it to be predominantly expressed in adipose tissue, with higher expression in visceral compared with subcutaneous adipose depots. Conclusion: SST in conjunction with cDNA microarray technology is a powerful tool to identify differentially expressed secreted proteins involved in complex diseases such as obesity and type 2 diabetes. Furthermore, a number of candidate genes were identified, in particular, Postn, which may have a role in the development of obesity and type 2 diabetes.

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Calsequestrin expression and calcium binding is increased in streptozotocin-induced diabetic rat skeletal muscle though not in cardiac muscle

Cited by 15 publications

References 50 publications

Expression of the skeletal muscle dystrophin–dystroglycan complex and syntrophin-nitric oxide synthase complex is severely affected in the type 2 diabetic Goto–Kakizaki rat

Expression of the skeletal muscle dystrophin–dystroglycan complex and syntrophin-nitric oxide synthase complex is severely affected in the type 2 diabetic Goto–Kakizaki rat

Polymorphism in the Calsequestrin 1 (CASQ1) Gene on Chromosome 1q21 Is Associated With Type 2 Diabetes in the Old Order Amish

Identification of secreted proteins associated with obesity and type 2 diabetes in Psammomys obesus

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