Summary
Cardiovascular disease represents the major cause of morbidity and mortality in noninsulin-dependent diabetic patients. While it was once thought that atherosclerotic vascular disease was responsible for all of these adverse effects, recent studies support the notion that one of the major adverse complications of diabetes is the development of a diabetic cardiomyopathy characterized by defects in both diastolic and systolic function. Contributing to the development of the cardiomyopathy is a shift in myosin isozyme content in favor of the least active V3 form. Also defective in the noninsulin-dependent diabetic heart is regulation of calcium homeostasis. While transport of calcium by the sarcolemmal and sarcoplasmic reticular calcium pumps are minimally affected by noninsulin-dependent diabetes, significant impairment occurs in sarcolemmal Na+-Ca2+ exchanger activity. This defect limits the ability of the diabetic heart to extrude calcium, contributing to an elevation in [Ca2+]i. Also promoting the accumulation of calcium by the diabetic cell is a decrease in Na+, K+ ATPase activity, which is known to increase [Ca2+]i secondary to a rise in [Na+]i. In addition, calcium influx via the calcium channel is stimulated. Although the molecular mechanisms underlying these defects are presently unknown, the possibility that they may be related to aberrations in glucose or lipid metabolism are considered. The evidence suggests that classical theories of glucose toxicity, such as excessive polyol production or glycosylation, appear to be insignificant factors in heart. Also insignificant are defects in lipid metabolism leading to accumulation of toxic lipid amphiphiles or triacylglycerol. Rather, the major defects involve membrane changes, such as phosphatidylethanolamine N-methylation and protein phosphorylation, which can be attributed to the state of insulin resistance.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Himsworth HP: Diabetes mellitus: Its differentiation into insulin-sensitive and insulin-insensitive types. Lancet 1: 117–120, 1936
Weir GC, Leahy JL, Bonner-Weir S: Experimental reduction of β-cell mass: implication for the pathogenesis of diabetes. Diabetes Metabol Rev 2: 125–161, 1986
Lipson LG: Diabetes in the elderly. Diagnosis, pathogenesis and therapy. Am J Med 80 (Supp. 5A): 10–21, 1986
Wilson PWF, Anderson KM, Kannel WB: Epidemiology of diabetes mellitus in the elderly: The Framingham study. Am J Med 80 (Supp. 5B): 3–9, 1986
DeFronzo RA: The triumvirate: β-cell, muscle, liver: A collusion responsible for NIDDM. Diabetes 37: 667–687, 1988
Coleman DL: Obese and diabetes: Two mutant genes causing diabetes-obesity syndromes in mice. Diabetologia 14: 141–148, 1978
Surwit RS, Feinglos MN, Livingston EG, Kuhn CM, McCubbin JA: Behavioral manipulation of the diabetic phenotype in ob/ob mice. Diabetes 33: 616–618, 1984
Kalderon B, Gutman A, Levy E, Shafrir E, Adler JH: Characterization of stages in development of obesity-diabetes syndrome in sand rat (Psammomys obesus). Diabetes 35: 717–724, 1986
Jeanrenaud B: Neuroendocrine and metabolic basis of type II diabetes as studied in animal models. Diabetes/Metabolism Reviews 4: 603–614, 1988
Slieker LJ, Roberts EF, Shaw WN, Johnson WT: Effect of streptozocin-induced diabetes on insulin-receptor tyrosine kinase activity in obese Zucker rats. Diabetes 39: 619–625, 1990
Bray GA: The Zucker fatty rat: a review. Fed Proc 36: 148–153, 1977
Weir GC, Clore ET, Zmachinski CJ, Bonner-Weir S: Islet secretion in a new experimental model for noninsulin-dependent diabetes. Diabetes 30: 590–595, 1981
Portha B, Picon L, Rosselin G: Chemical diabetes in the adult rat as the spontaneous evolution of neonatal diabetes. Diabetologia 17: 371–377, 1979
Portha B, Blondel O, Serradas P, McEvoy R, Giroix M-H, Kergoat M, Bailbe D: The rat models of non-insulin dependent diabetes induced by neonatal streptozotocin. Diabete & Metabolism 15: 61–75, 1989
Ward WK, Beard JE, Halter JB, Pfeifer MA, Porte D Jr: Pathophysiology of insulin secretion in non-insulin-dependent diabetes mellitus. Diabetes Care 7: 491–502, 1984
Steiner KE, Bowles CR, Mouton SM, Williams PE, Cherrington AD: The relative importance of first- and second-phase insulin secretion in countering the action of glucagon on glucose turnover in the conscious dog. Diabetes 31: 964–972, 1982
Giroix M-H, Portha B, Kergoat M, Bailbe D, Picon L: Glucose insensitivity and amino-acid hypersensitivity of insulin release in rats with non-insulin-dependent diabetes: A study with the perfused pancreas. Diabetes 32: 445–451, 1983
Blondel O, Bailbe D, Portha B: Relation of insulin deficiency to impaired insulin action in NIDDM adult rats given streptozocin as neonates. Diabetes 38: 610–617, 1989
Trent DF, Fletcher DJ, May JM, Bonner-Weir S, Weir GC: Abnormal islet and adipocyte function in young β-cell-deficient rats with near-normoglycemia. Diabetes 33: 170–175, 1984
Schaffer SW, Seyed-Mozaffari M, Cutcliff CR, Wilson GL: Postreceptor myocardial metabolic defect in a rat model of non-insulin-dependent diabetes mellitus. Diabetes 35: 593–597, 1986
Regan TJ: Congestive heart failure in the diabetic. Ann Rev Med 34: 161–168, 1983
Fein FS, Sonnenblick EH: Diabetic cardiomyopathy. Prog Cardiovasc Dis 27: 255–270, 1985
Tahiliani AG, McNeill JH: Diabetes-induced abnormalities in the myocardium. Life Sci 38: 959–974, 1986
Crepaldi G, Nosadini R: Diabetic cardiopathy: Is it a real entity? Diabetes/Metabolism Reviews 4: 273–288, 1988
Regan TJ, Lyons MM, Ahmed SS, Levinson GE, Oldewurtel HA, Ahmed MR, Haider B: Evidence for cardiomyopathy in familial diabetes mellitus. J Clin Invest 60: 885–899, 1977
Zoneraich S, Zoneraich O, Rhee JJ: Left ventricular performance in diabetic patients without clinical heart disease. Evaluation by systolic time intervals and echocardiography. Chest 72: 748–751, 1977
Uusitupa M, Siitonen O, Pyorala K, Lansimies E: Left ventricular function in newly diagnosed non-insulin-dependent (Type 2) diabetics evaluated by systolic time in tervals and echocardiography. Acta Med Scand 217: 379–388, 1985
Mustonen J, Laakso M, Uusitupa M, Sarlund H, Pyorala K, Rautio P, Kuikka J, Lansimies E: Improvement of left ventricular function after starting insulin treatment in patients with non-insulin-dependent diabetes. Diabetes Res 9: 27–30, 1988
Shapiro LM, Leatherdale BA, Coyne ME, Fletcher RF, Mackinnon J: Prospective study of heart disease in untreated maturity onset diabetes. Br Heart J 44: 342–348, 1980
Pozzoli G, Vitolo E, Collini P, DeMaria R, Castelli MR, Colombo F: Assessment of left ventricular function with M-mode echocardiography in a selected group of diabetic patients. Acta Diabet Lat 21: 71–84, 1984
Uusitupa M, Mustonen J, Laakso M, Vainio P, Lansimies E, Talwar S, Pyorala K: Impairment of diastolic function in middle-aged Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic patients free of cardiovascular disease. Diabetologia 31: 783–791, 1988
Stone PH, Muller JE, Hartwell T, York BJ, Rutherford JD, Parker CB, Turi ZG, Strauss HW, Willerson JT, Robertson T, Braunwald E, Jaffe AS: The effect of diabetes mellitus on prognosis and serial left ventricular function after acute myocardial infarction: Contribution of both coronary disease and diastolic left ventricular dysfunction to the adverse prognosis. J Am Coll Cardiol 14: 49–57, 1989
Randle PJ, Garland PB, Hales CN, Newsholme EA, Denton RM, Pogson CI: Interactions of metabolism and the physiological role of insulin. Rec Prog Hormone Res 22: 1–44, 1966
Wieland O, Siess E, Schulze-Wethmar FH, v. Funcke HG, Winton B: Active and inactive forms of pyruvate dehydrogenase in rat heart and kidney: Effect of diabetes, fasting and refeeding on pyruvate dehydrogenase interconversion. Arch Biochem Biophys 143: 593–601, 1971
Sale GJ, Randle PJ: Incorporation of [32P] Phosphate into the pyruvate dehydrogenase complex in rat heart mitochondria. Biochem J 188: 409–421, 1980
Kerbey AL, Randle PJ: Thermolabile factor accelerates pyruvate dehydrogenase kinase reaction in heart mitochondria of starved or alloxan-diabetic rats. FEBS Lett. 127: 188–192, 1981
Kobayashi K, Neely JR: Effects of increased cardiac work on pyruvate dehydrogenase activity in hearts from diabetis animals. J Mol Cell Cardiol 15: 347–357, 1983
Kerbey AL, Randle PJ, Kearns A: Dephosphorylation of pig heart pyruvate dehydrogenase phosphate complexes by pig heart pyruvate dehydrogenase phosphate phosphatase. Biochem J 195: 51–59, 1981
Teague WM, Pettit FH, Yeaman SJ, Reed LJ: Function of phosphorylation sites on pyruvate dehydrogenase. Biochem Biophys Res Commun 87: 244–252, 1979
Dennis SC, Padma A, DeBuysere MS, Olson MS: Studies on the regulation of pyruvate dehydrogenase in the isolated perfused rat heart. J Biol Chem 254: 1252–1258, 1979
Olson MS, Dennis SC, DeBuysere MS, Padma A: The regulation of pyruvate dehydrogenase in the isolated perfused rat heart. J Biol Chem 253: 7369–7375, 1978
Latipaa PM, Peuhkurinen KJ, Hiltunen JK, Hassinen IE: Regulation of pyruvate dehydrogenase during infusion of fatty acids of varying chain lengths in the perfused rat heart. J Mol Cell Cardiol 17: 1161–1171, 1985
Bunger R, Permanetter B: Parallel stimulation by Ca2+ of inotropism and pyruvate dehydrogenase in perfused heart. Am J Physiol 247: C45-C52, 1984
Kobayashi K, Neely JR: Mechanism of pyruvate dehydrogenase activation by increased cardiac work. J Mol Cell Cardiol 15: 369–382, 1983
Kerbey AL, Randle PJ, Cooper RH, Whitehouse S, Pask HT, Denton RM: Regulation of pyruvate dehydrogenase in rat heart. Biochem J 154: 327–348, 1976
Randle PJ, Kerbey AL, Espinal J: Mechanisms decreasing glucose oxidation in diabetes and starvation: Role of lipid fuels and hormones. Diabetes/Metabolism Reviews 4: 623–638, 1988
Kerbey AL, Vary TC, Randle PJ: Molecular mechanisms regulating myocardial glucose oxidation. Basic Res Cardiol 80, Suppl 2: 93–96, 1985
Sale GJ, Randle PJ: Occupancy of phosphorylation sites in pyruvate dehydrogenase phosphate complex in rat heartin vivo. Biochem J 206: 221–229, 1982
Paulson DJ, Crass MF III: Endogenous triacylglycerol metabolism in diabetic heart. Am J Physiol 242: H1084-H1094, 1982
Caterson ID, Williams PF, Kerbey AL, Astbury LD, Plehwe WE, Turtle JR: The effect of body weight and the fatty acid-oxidation inhibitor 2-tetradecylglycidic acid on pyruvate dehydrogenase complex activity in mouse heart. Biochem J 224: 787–791, 1984
Caterson ID, Kerbey AL, Cooney GJ, Frankland R, Denyer GS, Nicks J, Williams PF: Inactivation of pyruvate dehydrogenase complex in heart muscle mitochondria of gold-thioglucose-induced obese mice is not due to a stable increase in activity of pyruvate dehydrogenase kinase. Biochem J 253: 291–294, 1988
Bell GI, Kayano T, Buse JB, Burant CF, Takeda J, Lin D, Fukumoto H, Seino S: Molecular biology of mammalian glucose transporters. Diabetes Care 13: 198–208, 1990
Kasanicki MA, Pilch PF: Regulation of glucose-transporter function. Diabetes Care 13: 219–227, 1990
James DE, Brown R, Navarro J, Pilch PF: Insulin-regulatable tissues express a unique insulin-sensitive glucose transport protein. Nature 333: 183–185, 1988
Joost HG, Weber TM: The regulation of glucose transport in insulin-sensitive cells. Diabetologia 32: 831–838, 1989
Klip A, Paquet MR: Glucose transport and glucose transporters in muscle and their metabolic regulation. Diabetes Care 13: 228–243, 1990
Thorens B, Charron MJ, Lodish HF: Molecular physiology of glucose transporters. Diabetes Care 13: 209–218, 1990
Kahn BB, Charron MJ, Lodish HF, Cushman SW, Flier JS: Differential regulation of two glucose transporters in adipose cells from diabetic and insulin-treated diabetic rats. J Clin Invest 84: 404–411, 1989
Kuo TH, Moore KH, Giacomelli F, Wiener J: Defective oxidative metabolism of heart mitochondria from genetically diabetic mice. Diabetes 32: 781–787, 1983
Safer B, Williamson JR: Mitochondrial-cytosolic interactions in perfused rat heart: Role of coupled transamination in repletion of citric acid cycle intermediates. J Biol Chem 248: 2570–2579, 1973
Schaffer SW, Tan BH, Wilson GL: Development of a cardiomyopathy in a model of noninsulin-dependent diabetes. Am J Physiol 248: H179-H185, 1985
Schaffer SW, Mozaffari MS, Artman M, Wilson GL: Basis for myocardial mechanical defects associated with noninsulin-dependent diabetes. Am J Physiol 256: E25-E30, 1989
Penpargkul S, Schaible T, Scheuer J: The effect of diabetes on performance and metabolism of rat hearts. Circ Res 47: 911–921, 1980
Litwin SE, Raya TE, Anderson PG, Daugherty S, Goldman S: Abnormal cardiac function in the streptozotocin-diabetic rat: Changes in active and passive properties of the left ventricle. J Clin Invest 86: 481–488, 1990
Regan TJ, Lyons MM, Ahmed SS, Levinson GE, Oldewurtel HA, Ahmed MR, Haider B: Evidence for cardiomyopathy in familial diabetes mellitus. J Clin Invest 60: 885–899, 1977
Cobbold PH, Rink TJ: Fluorescence and bioluminescence measurement of cytoplasmic free calcium. Biochem J 248: 313–328, 1987
Dhalla NS, Pierce GN, Panagia V, Singal PK, Beamish RE: Calcium movements in relation to heart function. Basic Res Cardiol 77: 117–139, 1982
Langer GA, Frank JS, Philipson KD: Ultrastructure and calcium exchange of the sarcolemma, sarcoplasmic reticulum and mitochondria of the myocardium. Pharmacol Ther 6: 331–376, 1982
Wier WG: Cytoplasmic [Ca2+] in mammalian ventricle: Dynamic control by cellular processes. Ann Rev Physiol 52: 467–485, 1990
Mullins LJ: The generation of electric currents in cardiac fibers by Na/Ca exchange. Am J Physiol 236: C103-C110, 1979
Makino N, Dhalla KS, Elimban V, Dhalla NS: Sarcolemmal Ca2+ transport in streptozotocin-induced diabetic cardiomyopathy in rats. Am J Physiol 253: E202-E207, 1987
Ganguly PK, Pierce GN, Dhalla KS, Dhalla NS: Defective sarcoplasmic reticular calcium transport in diabetic cardiomyopathy. Am J Physiol 244: E528-E535, 1983
Lopaschuk GD, Tahiliani AG, Vadlamudi RVSV, Katz S, McNeill JH: Cardiac sarcoplasmic reticulum function in insulin- or carnitine-treated diabetic rats. Am J Physiol 245: H969-H976, 1983
Heyliger CE, Prakash A, McNeill JH: Alterations in cardiac sarcolemmal Ca2+ pump activity during diabetes mellitus. Am J Physiol 252: H540-H544, 1987
Sperelakis N: Regulation of calcium slow channels of cardiac muscle by cyclic nucleotides and phosphorylation. J Mol Cell Cardiol 20 (Supp. II): 75–105, 1988
Tsien RW, Bean BP, Hess P, Lansman JB, Nilius B, Nowycky MC: Mechanisms of calcium channel modulation by β-adrenergic agents and dihydropyridine calcium agonists. J Mol Cell Cardiol 18: 691–710, 1986
Hescheler J, Kameyama M, Trautwein W, Mieskes G, Soling H-D: Regulation of the cardiac calcium channel by protein phosphatases. Eur J Biochem 165: 261–266, 1987
Allo SN, Schaffer SW: Defective sarcolemmal phosphorylation associated with noninsulin-dependent diabetes. Biochim Biophys Acta 1023: 206–212, 1990
Imagawa T, Leung AT, Campbell KP: Phosphorylation of the 1,4-dihydropyridine receptor of the voltage-dependent Ca2+ channel by an intrinsic protein kinase in isolated triads from rabbit skeletal muscle. J Biol Chem 262: 8333–8339, 1987
Nobe S, Aomine M, Arita M, Ito S, Takaki R: Chronic diabetes mellitus prolongs action potential duration of rat ventricular muscles: Circumstantial evidence for impaired Ca2+ channel. Cardiovasc Res 24: 381–389, 1990
Alpert NR, Mulieri LA: Functional consequences of altered cardiac myosin isoenzymes. Med Sci Sports Exerc 18: 309–313, 1986
Hoh JFY, McGrath PA, Hale PT: Electrophoretic analysis of multiple forms of rat cardiac myosin: Effects of hypophysectomy and thyroxine replacement. J Mol Cell Cardiol 10: 1053–1076, 1977
Malhotra A, Karell M, Scheuer J: Multiple cardiac contractile protein abnormalities in myopathic Syrian hamsters (Bio 53:58). J Mol Cell Cardiol 17: 95–107, 1985
Wikman-Coffelt J, Sievers R, Parmley WW: Influence of myocardial isomyosins on cardiac performance and oxygen consumption. Biochem Biophys Res Commun 130: 1314–1323, 1985
Horowitz M, Peyser YM, Muhlrad A: Alterations in cardiac myosin isoenzymes distribution as an adaptation to chronic environmental heat stress in the rat. J Mol Cell Cardiol 18: 511–515, 1986
Takeda N, Ohkubo T, Hatanaka T, Takeda A, Nakamura I, Nagano M: Myocardial contractility and left ventricular myosin isoenzyme pattern in cardiac hypertrophy due to chronic volume overload. Basic Res Cardiol 82 (Supp. 2): 215–221, 1987
Lecarpentier Y, Vugaisky LB, Chemla D, Mercadier JJ, Schwartz K, Whalen RG, Martin JL: Coordinated changes in contractility, energetics, and isomyosins after aortic stenosis. Am J Physiol 252: H275-H282, 1987
Pierce GN, Dhalla NS: Cardiac myofibrillar ATPase activity in diabetic rats. J Mol Cell Cardiol 13: 1063–1069, 1981
Malhotra A, Penpargkul S, Fein FS, Sonnenblick EH, Scheuer J: The effect of streptozotocin-induced diabetes in rats on cardiac contractile proteins. Circ Res 49: 1243–1250, 1981
Dillmann WH: Influence of thyroid hormone administration on myosin ATPase activity and myosin isoenzyme distribution in the heart of diabetic rats. Metabolism 31: 199–204, 1982
Garber DW, Everett AW, Neely JR: Cardiac function and myosin ATPase in diabetic rats treated with insulin, T3 and T4. Am J Physiol 244: H592-H598, 1983
Pollack PS, Malhotra A, Fein FS, Scheuer J: Effects of diabetes on cardiac contractile proteins in rabbits and reversal with insulin. Am J Physiol 251: H448-H454, 1986
Mozaffari MS, Allo S, Schaffer SW: The effect of sulfonylurea therapy on defective calcium movement associated with diabetic cardiomyopathy. Can J Physiol Pharmacol 67: 1431–1436, 1989
Dillmann WH: Fructose feeding increases Ca2+-activated myosin ATPase activity and changes myosin isoenzyme distribution in the diabetic rat heart. Endocrinology 114: 1678–1685, 1984
Dillmann WH: Methyl palmoxirate increases Ca2+-myosin ATPase activity and changes myosin isoenzyme distribution in the diabetic rat heart. Am J Physiol 248: E602-E606, 1985
Dillmann WH: Myosin isoenzyme distribution and Ca2+-activated myosin ATPase activity in the rat heart is influenced by fructose feeding and triiodothyronine. Endocrinology 116: 2160–2166, 1985
Paulson DJ, Kopp SJ, Peace DG, Tow JP: Myocardial adaptation to endurance exercise training in diabetic rats. Am J Physiol 252: R1073-R1081, 1987
Takeda N, Nakamura I, Ohkubo T, Hatanaka T, Nagano M: Effects of physical training on the myocardium of streptozotocin-induced diabetic rats. Bas Res Cardiol 83: 525–530, 1988
Fein FS, Malhotra A, Miller-Green B, Scheuer J, Sonnenblick EH: Diabetic cardiomyopathy in rats: Mechanical and chemical response to different insulin doses. Am J Physiol 247: H817-H823, 1984
Tahiliani AG, McNeill JH: Effects of triiodothyronine and carnitine therapy on myocardial dysfunction in diabetic rats. Can J Physiol Pharmacol 64: 669–672, 1986
Xiang H, Heyliger CE, McNeill JH: Effect of myo-inositol and T3 on myocardial lipids and cardiac function in streptozocin-induced diabetic rats. Diabetes 37: 1542–1548, 1988
Uusitupa M, Siitonen O, Aro A, Korhoer T, Pyorala K: Effect of correction of hyperglycemia on left ventricular function in non-insulin-dependent (type 2) diabetics. Acta Med Scand 213: 363–368, 1983
Kador PF, Kinoshita JH: Role of aldose reductase in the development of diabetes-associated complications. Am J Med 79 (Supp. 5A): 8–12, 1985
Fagius J, Brattberg A, Jameson S, Berne C: Limited benefit of treatment of diabetic polyneuropathy with an aldose reductase inhibitor: A 24 week controlled trial. Diabetologia 28: 323–329, 1985
Beyer-Mears A: The polyol pathway, sorbinil and renal dysfunction. Metabolism 35 (Supp. 1): 46–54, 1986
Engerman RL, Kern TS: Hyperglycemia as a cause of diabetic retinopathy. Metabolism 35 (Supp. 1): 20–23, 1986
Pfeifer MA: Clinical trials of sorbinil on nerve function. Metabolism 35 (Supp. 1): 78–82, 1986
Kador PF: The role of aldose reductase in the development of diabetic complications. Med Res Rev 8: 325–352, 1988
Bank N, Mower P, Aynedjian HS, Wilkes BM, Silverman S: Sorbinil prevent glomerular hyperfusion in diabetic rats. Am J Physiol 256: 171000–171006, 1989
Roy TM, Broadstone VL, Peterson HR, Snider HL, Cyrus J, Fell R, Rothchild AH, Samols E, Pfeifer MA: The effect of an aldose reductase inhibitor on cardiovascular performance in patients with diabetes mellitus. Diabetes Res Clin Practice 10: 91–97, 1990
Cameron NE, Cotter MA, Robertson S: Contractile properties of cardiac papillary muscle in streptozotocin-diabetic rats and the effects of aldose reductase inhibition. Diabetologia 32: 365–370, 1989
Greene DA, Lattimer SA, Sima AAF: Sorbitol, phosphoinositides and sodium-potassium ATPase in the pathogenesis of diabetic complications. New Eng J Med 316: 599–606, 1987
Greene DA, Lattimer SA, Sima AAF: Are disturbances of sorbitol, phosphoinositide, and Na+-K+-ATPase regulation involved in pathogenesis of diabetic neuropathy? Diabetes 37: 688–693, 1988
Berge C-H, Hjalmarson A, Sjogren K-G, Jacobsson B: The effect of diabetes on phosphatidylinositol turnover and calcium influx in myocardium. Horm Metabol Res 20: 381–386, 1988
Farese RV, Cooper DR: Potential role of phospholipid-signaling systems in insulin action and states of clinical insulin resistance. Diabetes/Metabolism Rev 5: 455–474, 1989
Kennedy L, Baynes JW: Non-enzymatic glycosylation and the chronic complications of diabetes: An overview. Diabetologia 26: 93–98, 1984
Kirschenbaum DM: Glycosylation of proteins: Its implications in diabetic control and complications. Ped Clinics North America 31: 611–621, 1984
Brownlee M, Cerami A, Vlassara H: Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. New Eng J Med 318: 1315–1321, 1988
Brownlee M, Cerami A: The biochemistry of the complications of diabetes mellitus. Ann Rev Biochem 50: 385–432, 1981
Ganguly PK, Thliveris JA, Mehta A: Evidence against the involvement of nonenzymatic glycosylation in diabetic cardiomyopathy. Metabolism 39: 769–773, 1990
Serrano MA, Cabezas JA, Reglero A: Carbohydrate contents and glycosidase and glycosyl transferase activities in tissues from streptozotocin diabetic mice. Comp Biochem Physiol 80: 629–632, 1985
Feuvray D, Idell-Wenger JA, Neely JR: Effects of ischemia on rat myocardial function and metabolism in diabetes. Circ Res 44: 322–329, 1979
Katz AM, Messineo FC: Lipid-membrane interactions and the pathogenesis of ischemic damage in the myocardium. Circ Res 48: 1–16, 1981
Corr PB, Gross RW, Sobel BE: Amphipathic metabolites and membrane dysfunction in ischemic myocardium. Circ Res 55: 135–154, 1984
Lopaschuk GD, Katz S, McNeill JH: The effect of alloxan- and streptozotocin-induced diabetes on calcium transport in rat cardiac sarcoplasmic reticulum. The possible involvement of long chain acylcarnitines. Can J Physiol Pharmacol 61: 439–448, 1983
Holman RT, Johnson SB, Gerrard JM, Mauer SM, Kupcho-Sandberg S, Brown DM: Arachidonic acid deficiency in streptozotocin-induced diabetes. Proc Natl Acad Sci USA 80: 2375–2379, 1983
Gudbjarnason S, El-Hage AN, Whitehurst VE, Simental F, Balazs T: Reduced arachidonic acid levels in major phospholipids of heart muscle in the diabetic rat. J Mol Cell Cardiol 19: 1141–1146, 1987
Horrobin DF: The roles of essential fatty acids in the development of diabetic neuropathy and other complications of diabetes mellitus. Prostaglandins Leukotr Ess Fatty Acids 31: 181–197, 1988
Black SC, Katz S, McNeill JH: Cardiac performance and plasma lipids of omega-3 fatty acid-treated streptozocininduced diabetic rats. Diabetes 38: 969–974, 1989
Brenner RR: Effect of unsaturated fatty acids in membrane structure and enzyme kinetics. Prog Lipid Res 23: 69–96, 1984
Stubbs CD, Smith AD: The modification of mammalian membrane polyunsaturated fatty acid composition in relation to membrane fluidity and function. Biochim Biophys Acta 779: 89–137, 1984
Ganguly PK, Rice KM, Panagia V, Dhalla NS: Sarcolemmal phosphatidylethanolamine N-methylation in diabetic cardiomyopathy. Circ Res 55: 504–512, 1984
Gupta MP, Panagia V, Dhalla NS: Phospholipid N-methylation-dependent alterations of cardiac contractile function by L-methionine. J Pharmacol Exp Therap 245: 664–672, 1988
Oberley LW: Free radicals and diabetes. Free Rad Biol Med 5: 113–124, 1988
Wohaieb SA, Godin DV: Alterations in tissue antioxidant systems in the spontaneously diabetic (BB Wistar) rat. Can J Physiol Pharmacol 65: 2191–2195, 1987
Wohaieb SA, Godin DV: Alterations in free radical tissue-defense mechanisms in streptozocin-induced diabetes in rat: effects on insulin treatment. Diabetes 36: 1014–1018, 1987
Matkovics B, Varga SI, Szabo L, Witas H: The effect of diabetes on the activities of the peroxide metabolism enzymes. Horm Metabol Res 14: 77–79, 1982
Ganguly PK, Dhalla KS, Innes IR, Beamish RE, Dhalla NS: Altered norepinephrine turnover and metabolism in diabetic cardiomyopathy. Circ Res 59: 684–693, 1986
Pieper GM: Arachidonic acid causes postischemic dysfunction in control but not diabetic hearts. Am J Physiol 258: H923-H930, 1990
Zick Y: The insulin receptor: Structure and function. Critical Rev Biochem Mol Biol 24: 217–269, 1989
Van de Werve G, Zaninetti D, Lang U, Vallotton MB, Jeanrenaud B: Identification of a major defect in insulin-resistant tissues of genetically obese (fa/fa) rats: Impaired protein kinase C. Diabetes 36: 310–314, 1987
Okumura K, Akiyama N, Hashimoto H, Ogawa K, Satake T: Alteration of 1,2-diacylglycerol content in myocardium from diabetic rats. Diabetes 37: 1168–1172, 1988
Yuan S, Sunahara FA, Sen AK: Tumor-promoting phorbol esters inhibit cardiac functions and induce redistribution of protein kinase C in perfused beating rat heart. Circ Res 61: 372–378, 1987
Keely SL, Corbin JD, Park CR: Regulation of adenosine 3′:5′-monophosphate-dependent protein kinase: Regulation of the heart enzyme by epinephrine, glucagon, insulin and 1-methyl-3-isobutylxanthine. J Biol Chem 250: 4832–4840, 1975
Miller TB Jr: Phosphorylase activation hypersensitivity in hearts of diabetic rats. Am J Physiol 246: E134-E140, 1984
Ingebritsen TS, Stewart AA, Cohen P: The protein phosphatases involved in cellular regulation: 6. Measurement of type-1 and type-2 protein phosphatases in extracts of mammalian tissues; an assessment of their physiological roles. Eur J Biochem 132: 297–307, 1983
Miller TB Jr: A dual role for insulin in the regulation of cardiac glycogen synthase. J Biol Chem 253: 5389–5394, 1978
Mumby M, Russell KL, Garrard LJ, Green DD: Cardiac contractile protein phosphatases: Purification of two enzyme forms and their characterization with subunit-specific antibodies. J Biol Chem 262: 6257–6265, 1987
Chisholm AAK, Cohen P: The myosin-bound form of protein phosphatase 1 (PP-1M) is the enzyme that dephosphorylates native myosin in skeletal and cardiac muscles. Biochim Biophys Acta 971: 163–169, 1988
Iyer RB, Koritz SB, Kirchberger MA: A regulation of the level of phosphorylated phospholamban by inhibitor-1 in rat heart preparationsin vivo. Mol Cell Endocrinol 55: 1–6, 1988
Kranias EG, Steenaart NAE, DiSalvo J: Purification and characterization of phospholamban phosphatase from cardiac muscle. J Biol Chem 263: 15681–15687, 1988
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Schaffer, S.W. Cardiomyopathy associated with noninsulin-dependent diabetes. Mol Cell Biochem 107, 1–20 (1991). https://doi.org/10.1007/BF02424571
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02424571