Reaction of rabbit skeletal myosin with D‐glucose 6‐phosphate

Avigad, Gad; Kniep, Annemarie C.; Bailin, Gary

doi:10.1080/15216549600201762

Cited by 25 publications

(28 citation statements)

References 18 publications

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“…Thus the milieu within the pancreatic -cells appears to represent a particularly favourable environment for the glycation of insulin , 1997a. This might reflect the fact that glucose is efficiently transported into the -cell by GLUT transporters and rapidly metabolized by glucokinase to the particularly potent glycating agent glucose-6-phosphate (Leahy 1990, Flatt 1992, Avigad et al 1996, Abdel-Wahab et al 1997a, O' Harte et al 1997). Since glycated insulin has been shown to exhibit reduced bioactivity and glucoselowering ability (Dolhofer & Wieland 1979, Lapolla et al 1988, Hunter et al 1996, Abdel-Wahab et al 1997b, an involvement in the glucose toxicity, insulin resistance and glucose intolerance of type 2 diabetes has been postulated (Flatt et al 1994.…”

Section: Discussionmentioning

confidence: 99%

Production and characterization of specific antibodies for evaluation of glycated insulin in plasma and biological tissues

McKillop¹,

McCluskey²,

Boyd³

et al. 2000

Journal of Endocrinology

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Previous studies have shown that glycation of insulin occurs in pancreatic -cells under conditions of hyperglycaemia and that the site of glycation is the N-terminal Phe 1 of the insulin B-chain. To enable evaluation of glycated insulin in diabetes, specific antibodies were raised in rabbits and guinea-pigs by using two synthetic peptides (A: Phe-Val-Asn-Gln-His-Leu-Cys-Tyr, and B: Phe-ValAsn-Gln-His-Leu-Tyr-Lys) modified by N-terminal glycation and corresponding closely to the N-terminal sequence of the glycated human insulin B-chain. For immunization, the glycated peptides were conjugated either to keyhole limpet haemocyanin or ovalbumin using glutaraldehyde, m-maleimidobenzoyl-N-hydroxysuccinimide ester or 1-ethyl-3-(3-dimethylamino propyl) carbodiimide hydrochloride. Antibody titration curves, obtained using I 125 -tyrosylated tracer prepared from glycated peptide A, revealed high-titre antisera in five groups of animals immunized for 8-28 weeks. The highest titres were observed in rabbits and guinea-pigs immunized with peptide B coupled to ovalbumin using glutaraldehyde. Under radioimmunoassay conditions, these antisera exhibited effective dose (median) (ED 50 ) values for glycated insulin of 0·3-15 ng/ml and 0·9-2·5 ng/ml respectively, with negligible cross-reactivity against insulin or other islet peptides. The degree of cross-reaction with glycated proinsulin was approximately 50%. Glycated insulin in plasma of control and hydrocortisone-treated diabetic rats measured using rabbit 3 antiserum (1:10 000 dilution; sensitivity <19 pg/ml) was 0·08 0·01 and 1·5 0·6 ng/ ml (P<0·01), corresponding to 4 and 16% of total circulating insulin concentration respectively. Immunocytochemistry studies of the pancreas of streptozotocin-treated diabetic rats using a 1:1000 dilution of guinea-pig 2 antiserum revealed clusters of fluorescent positively stained cells in islets. These studies document the successful production of polyclonal antisera specific for glycated insulin and their usefulness in radioimmunoassays and immunocytochemistry. The demonstration of glycated insulin in plasma and islets of animal models of diabetes supports the view that glycation of insulin is involved in the pathogenesis of this disease.

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Section: Discussionmentioning

confidence: 99%

Production and characterization of specific antibodies for evaluation of glycated insulin in plasma and biological tissues

McKillop¹,

McCluskey²,

Boyd³

et al. 2000

Journal of Endocrinology

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“…It is likely to follow from glucose transporter-mediated entry into the ␤-cell and rapid metabolism by glucokinase to glucose-6-phos- phate (41), which is a particularly potent glycating agent (42,43). This is in turn transported to the inner leaflet of the endoplasmic reticulum membrane by glucose-6-phosphatase (44), where proinsulin and insulin are produced at high concentrations for incorporation into vesicles for transport to the Golgi for packaging into secretory granules, where storage and further processing take place (45).…”

Section: Discussionmentioning

confidence: 99%

Demonstration of Glycated Insulin in Human Diabetic Plasma and Decreased Biological Activity Assessed by Euglycemic-Hyperinsulinemic Clamp Technique in Humans

et al. 2003

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. Measurement of glycated insulin in plasma of type 2 diabetic subjects by specific RIA gave circulating levels of 10.1 ؎ 2.3 pmol/l, corresponding to ϳ9% total insulin. Biological activity of pure synthetic monoglycated insulin (insulin B-chain Phe 1 -glucitol adduct) was evaluated in seven overnight-fasted healthy nonobese male volunteers using two-step euglycemichyperinsulinemic clamps (2 h at 16.6 g ⅐ kg ؊1 ⅐ min ؊1 , followed by 2 h at 83.0 g ⅐ kg ؊1 ⅐ min ؊1 ; corresponding to 0.4 and 2.0 mU ⅐ kg ؊1 ⅐ min ؊1 ). At the lower dose, the exogenous glucose infusion rates required to maintain euglycemia during steady state were significantly lower with glycated insulin (P < 0.01) and ϳ70% more glycated insulin was required to induce a similar rate of insulin-mediated glucose uptake. Maximal responses at the higher rates of infusion were similar for glycated and control insulin. Inhibitory effects on endogenous glucose production, insulin secretion, and lipolysis, as indicated by measurements of C-peptide, nonesterified free fatty acids, and glycerol, were also similar. Receptor binding to CHO-T cells transfected with human insulin receptor and in vivo metabolic clearance revealed no differences between glycated and native insulin, suggesting that impaired biological activity is due to a postreceptor effect. The present demonstration of glycated insulin in human plasma and related impairment of physiological insulin-mediated glucose uptake suggests a role for glycated insulin in glucose toxicity and impaired insulin action in type 2 diabetes. Diabetes 52:492-498, 2003

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“…As regards other post-translational modifications, although it has been suggested that myosin function could be affected by glycation [1,70] or deamination [2], evidence remains preliminary. A direct effect of oxidants on contractile proteins has recently been suggested [23] and the issue is worthy of being further explored.…”

Section: Post-translational Modifications Of Myosinmentioning

confidence: 99%

Functional heterogeneity of mammalian single muscle fibres: do myosin isoforms tell the whole story?

Bottinelli

2001

Pflügers Arch - Eur J Physiol

197

185

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The large amount of data published in the last 10-15 years indicate that myosin isoforms are the major determinant of the large functional heterogeneity of the key contractile and biochemical properties of skeletal muscle fibres, including velocity of shortening, ATP consumption and power. Recent evidences are difficult to reconcile with such an idea and suggest that the properties of muscle fibres that are likely to depend on myosin, such as velocity of shortening, can change without a change in myosin isoform. That a given myosin isoform can modify its properties without shifting to another isoform is confirmed by some analyses of isolated myosin in vitro. The present review is mainly focused on findings that challenge the role of myosin isoforms in determining the functional heterogeneity of skeletal muscle. The work also reports on potential mechanisms behind such changes in myosin function independent of a shift in myosin isoform: the coexistence of different myosin heavy chain (MHC) isoforms in the same fibre, the existence of as yet undetected MHC isoforms, myosin light chain isoforms, post-translational modifications of myosin, the role of other myofibrillar proteins, geometry of the sarcomere and the myosin concentration in single fibres.

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Reaction of rabbit skeletal myosin with D‐glucose 6‐phosphate

Cited by 25 publications

References 18 publications

Production and characterization of specific antibodies for evaluation of glycated insulin in plasma and biological tissues

Production and characterization of specific antibodies for evaluation of glycated insulin in plasma and biological tissues

Demonstration of Glycated Insulin in Human Diabetic Plasma and Decreased Biological Activity Assessed by Euglycemic-Hyperinsulinemic Clamp Technique in Humans

Functional heterogeneity of mammalian single muscle fibres: do myosin isoforms tell the whole story?

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