THE SPINY MOUSE: IN SEARCH OF AN ANIMAL MODEL FOR PATHOGENESIS OF TYPE 2 DIABETES MELLITUS
In: Israel Journal of Ecology and EvolutionSearch for other papers by RAFAEL NESHER in
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Search for other papers by EROL CERASI in
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We review the data suggesting that the spiny mouse Acomys cahirinus may be a suitable model for the early stages of the development of Type 2 diabetes mellitus in man. When raised under laboratory conditions, A. cahirinus develops glucose intolerance, obesity, and varying degrees of insulin resistance. As in Type 2 diabetes, it exhibits a reduced glucose clearance rate (Kg) following an IV glucose challenge, deficient β-cell sensitivity to glucose (Km), but no change in its capacity to secrete insulin (Vmax). Its islets are well granulated with processed insulin, but, as in Type 2 diabetes, an intrinsic defect in β-cell stimulus-secretion coupling hinders the ability to meet the increasing peripheral demand for insulin caused by the developing obesity. In vitro studies with isolated islets resemble whole animal studies: a reduced early-phase insulin response to glucose (decreased Vmax), delayed and deficient late-phase response, and increased Km indicative of reduced sensitivity to glucose. We demonstrated a defective link between glycolysis, the initial step in the glucose-dependent stimulus-secretion coupling and adenylyl cyclase, a major stimulus-amplifying signaling branch, as well as a defective “readout” of the cyclic AMP signal. Additional stimulus-secretion loci are probably involved in the defective β-cell response to glucose. An integrated model for the pathogenesis of Type 2 diabetes is presented.
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-
Alcolado J.C., Alcolado R.Importance of maternal history of non-insulin dependent diabetic patients Br. Med. J 1991 302 1178 80
-
Ammala C, Ashcroft F.M., Rorsman P.Calcium-independent potentiation of insulin release by cyclic AMP in single beta-cells Nature 1993 363 356 358
-
Ashcroft F.M., Ashcroft S.J.H., Mechanism of insulin secretion. InsulIn: Molecular biology to pathology; a practical approach Ashcroft F.M., Ashcroft S.J.H.Oxford University Press London 1992 97 139
-
Bone A.J., Animal models of insulin-dependent diabetes mellitus. Textbook of diabetes Pickup J.C., Williams G.Blackwell Scientific Publications Oxford 1991 151 163
-
Boner-Weir S., Leahy J.L., Weir G.C., Induced rat models of non-insulin dependent diabetes. Lessons from animal diabetes. Libbey, London Shafrir E., Renold A.E.1988 295 300
-
Calle R., Ganesan S., Smallwood J.I., Rasmussen H.Glucose-induced phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) in isolated rat pancreatic islets J. Biol. Chem 1992 267 18723 18727
-
Cameron D.P., Stauffacher W., Orci L., Amherdt M., Renold A.E.Defective immunoreative insulin secretion in the Acomys cahirinus Diabetes 1972 21 1060 1071
-
Cerasi E.Potentiation of insulin release by glucose in man III Normal recognition of glucose as potentiator in subjects with low insulin response and mild diabetes. Acta Endocrinol. (Copenhagen) 1975 79 511 537
-
Cerasi E., Aetiology of type II diabetes. InsulIn: Molecular biology to pathology; a practical approach Ashcroft F., Ashcroft S.Oxford University Press London 1992 347 381
-
Cerasi E., Luft R., Efendic S.Decreased sensitivity of the pancreatic beta cells to glucose in prediabetic and diabetic subjects A glucose dose-response study. Diabetes 1972 21 224 234
-
Chou H.F., Ipp E.Pulsatile insulin secretion in isolated rat islets Diabetes 1990 39 112 117
-
Chou H.F., Berman N., Ipp E.Oscillations of lactate released from islets of langerhans: evidence for oscillatory glycolysis in β-cells Am. J. Physiol 1992 262 E800 805
-
Cohen M.P., Stern E., Rusecki Y., Zeidler A.High prevalence of diabetes in young adult Ethiopian immigrants to Israel Diabetes 1988 37 824 828
-
DeFronzo R.A., Bonadonna R.C., Ferrannini E.Pathogenesis of NIDDM: A balanced overview Diabetes Care 1992 15 318 368
-
Dormán J.S.Genetic epidemiology of insulin-dependent diabetes mellitus: international comparisons using molecular genetics Ann. Med 1992 24 393 399
-
Fujimoto W.Y., Newell M.L., Grote M., Bergstrom R.W., Shuman W.P.Visceral fat obesity and morbidity: NIDDM and atherogenic risk in Japanese American men and women Int. J. Obes 1991 2 41 44
-
Garcia-Hermida O., Gomez-Aceb J.A different pattern of insulin release in perfused islets of the rabbit Biochem. Biophys. Res. Commun 1974 57 209 215
-
Gauguier D., Bihoreau M.T., Ktorza A., Berthault M.F., Picon L.Inheritance of diabetes mellitus as consequence of gestational hyperglycemia in rats Diabetes 1990 39 734 739
-
Gonet A.E., Stauffacher W., Pictet R., Mougin J., Renold A.E.Obesity and diabete mellitus with striking congenital hyperplasia of the islets of Langerhans in spiny mice (Acomys cahirinus) I. Histological findings and preliminary metabolic observations. Diabetologia 1965 1 162 166
-
Grapengiesser E., Gylfe E., Hellman B.Cyclic AMP as a determinant for glucose induction of fast Ca2+ oscillations in isolated pancreatic beta-cells J. Biol. Chem 1991 266 12207 12210
-
Grill V., Cerasi E.The metabolism of cyclic AMP and glucose in isolated islets from Acomys cahirinus Diabetologia 1979 16 47 50
-
Grill V., Rundfeldt M.Abnormalities of insulin response after ambient and previous exposure to glucose in streptozotocin diabetic and dexamethasone treated rats Role of hyperglycaemia and increased B cell demand. Diabetes 1986 35 44 51
-
Gutzeit A., Rabinovitch A., Karakash C., Stauffacher W., Renold A.E., Cerasi E.Acomys cahirinus). Diabetologia 10 (Suppl): 1974a 661 665Evidence for decreased sensitivity to glucose of isolated islets from spiny mice
-
Gutzeit A., Rabinovitch A., Studer P.P., Truehart P.A., Cerasi E., Renold A.E.Decreased intravenous glucose tolerance and low plasma insulin response in spiny mice (Acomys cahirinus) Diabetologia 1974b 10 667 670
-
Gutzeit A., Renold A.E., Cerasi E., Shafrir E.Effect of diet-induced obesity on glucose and insulin tolerance of a rodent with a low insulin response (Acomys cahirinus) Diabetes 1979 28 777 784
-
Gylfe E.Nutrient secretagogues induce bimodal early changes in cytoplasmic calcium of insulin-releasing ob/ob mouse beta-cells J. Biol. Chem 1988 263 13750 13754
-
Hales C.N., Barker J.Type 2 (non-insulin dependent) diabetes mellitus: the thrifty phenotype hypothesis Diabetologia 1992 35 595 601
-
Hansen B.D., Jen K.L.C., Pek S.B., Wolfe R.A.Rapid oscillation in plasma insulin, glucagon and glucose in obese and normal weight humans J. Clin. Endocrinol. Metab 1982 54 785 792
-
Hayek A.Preservation of insulin release from individual islets of obese Zocke rats Horm. Metab. Res 1981 13 119 120
-
Hellman B., Gylfe E., Grapengiesser E., Lund P.-E., Berts A.Cytoplasmic Ca2t oscillations in pancreatic b-cells Biochim. Biophys. Acta 1992 1113 295 305
-
Henquin J.C.Relative importance of extracellular and intracellular calcium for the two phases of glucose-stimulated insulin release: studies with theophylline Endocrinology 1978 102 723 730
-
Henquin J.C., Meissner H.P.Significance of ionic fluxes and changes in membrane potential for stimulus-secretion coupling in pancreatic B-cells Experientia 1984 40 1043 1052
-
Hermans M.P., Henquin J.C.Relative importance of extracellular and intracellular Ca2+ for acetylcholine stimulation of insulin release in mouse islets Diabetes 1989 38 198 204
-
Hitman G.A., Genetics of non-insulin-dependent diabetes mellitus. Textbook of diabetes Pickup J.C., Williams G.Blackwell Scientific Publications Oxford 1991 172 180
-
Hopkins W.F., Fatherazi S., Peter R.B., Corkey B.E., Cook D.L.Two sites for adenine—nucleotide regulation of ATP-sensitive potassium channels in mouse pancreatic beta-cells and HIT cells J. Membr. Biol 1992 129 287 295
-
Howell S.L., Insulin biosythesis and secretion. Textbook of diabetes Pickup J.C., Williams G.Blackwell Scientific Publications Oxford 1991 72 83
-
Hughes S.J., Smith H., Ashcroft S.J.Characterization of Ca2+/calmodulin-dependent protein kinase in rat pancreatic islets Biochem. J 1993 289 795 800
-
Iselius L., Lindsten J., Morton N.E., Efendic S., Cerasi E., Haegermark A., Luft R.Evidence for an autosomal recessive gene response to glucose in man Clin. Genet 1982 22 180 194
-
Iselius L., Lindsten J., Morton N.E., Efendic S., Cerasi E., Haegermark A., Luft R.Genetic regulation of the kinetics of glucose-induced insulin release in man Clin. Genet 1985 28 8 15
-
Jarrett R.J., The epidemology of diabetes mellitus. Textbook of diabetes Pickup J.C., Williams G.Blackwell Scientific Publications Oxford 1991 47 56
-
Jaspan J.B., Lever K.S., Polonsky K.S., Van Cauter E.In vivo pulsatility of pancreatic islet peptides Am. J. Physiol 1986 251 E215 226
-
Knowler W.C., Pettitt DJ., Saad M.F., Bennett P.H.Diabetes mellitus in the Pima Indians: incidence, risk factors and pathogenesis Diabetes Metab. Rev 1990 6 1 27
-
Kobberling J., Tillil H.Genetic and nutritional factors in the etiology and pathogenesis of diabetes mellitus World Rev. Nutr. Diet 1990 63 102 115
-
Lang D.A., Matthews D.R., Burnett M., Ward G.M., Turner R.C.Pulsatile synchronous basal insulin and glucagon secretion in man Diabetes 1982 31 22 26
-
Lean M.E., Mann J.I., Obesity, body fat distribution and diet in the aetiology of non—insulin-dependent diabetes meillitus. Textbook of diabetes Pickup J.C., Williams G.Blackwell Scientific Publications Oxford 1991 181 191
-
Lindstein J., Cerasi E., Luft R., Morton N.E., Ryman N.Significance of genetic factors for the plasma insulin response to glucose in healthy subjects Clin. Genet 1976 10 125 134
-
Longo E.A., Tornheim K., Deeney J.T., Varnum B.A., Tillotson D., Prentki M., Corkey B.E.Oscillations in cytosolic free Ca2+, oxygen consumption, and insulin secretion in glucose-stimulated rat pancreatic islets J. Biol. Chem 1991 266 9314 9319
-
Martinez N.C.Diabetes and minority populations Focus onMexican Americans. Nurs. Clin. North Am 1993 28 87 95
-
Nesher R., Cerasi E.Biphasic insulin release as the expression of combined inhibitory and potentiating effects of glucose Endocrinology 1987 121 1017 1024
-
Nesher R., Tuch B., Hage C, Levy J., Cerasi E.Time-dependent inhibition of insulin release: suppression of the arginine effect by hyperglycaemia Diabetologia 1984 26 142 145
-
Nesher R., Abramovitch E., Cerasi E.Correction of diabetic pattern of insulin release from islets of the spiny mouse (Acomys cahirinus) by glucose priming in vitro Diabetologia 1985 28 233 236
-
Nesher R., Abramovitch E., Cerasi E.Reduced early and late phase insulin response to glucose in isolated spiny mouse (Acomys cahirinus) islets: a defective link between glycolysis and adenylate cyclase Diabetologia 1989a 32 644 648
-
Nesher R., Eylon L., Segal N., Cerasi E.β-cell memory to insulin secretagogues: Characterization of the time-dependent inhibitory control system in isolated rat pancreas Endocrinology 1989b 124 142 148
-
Niki I., Tamagawa T., Niki H., Niki A., Koide T., Sakamoto N.Possible involvement of diacylglycerol-activated Ca2+-dependent protein kinase in glucose memory of rat pancreatic B-cell Acta Endocrinol. (Copenhagen) 1988 118 204 208
-
O'Meara N.M., Sturis J., Van C.E., Polonsky K.S.Lack of control by glucose of ultradian insulin secretory oscillations in impaired glucose tolerance and in non-insulin—dependent diabetes mellitus J. Clin. Invest 1993 92 262 271
-
O'Rahilly S., Turner R.C., Matthews D.R.Impaired pulsatile secretion of insulin in relatives of patients with non-insulin-dependent diabetes N. Engl. J. Med 1988 318 1225 1230
-
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 Metab 1989 15 61 75
-
Rabinovitch A., Gutzeit A., Grill V., Kikuchi M., Renold A.E., Cerasi E.Defective insulin secretion in the Spiny mouse (Acomys cahirinus) Possible value in the study of the pathophysiology of diabetes. Isr. J. Med. Sci 1975a 11 730 737
-
Rabinovitch A., Gutzeit A., Kikuchi M., Cerasi E., Renold A.E.Defective early phase insulin release in perifused isolated pancreatic islets of spiny mice (Acomys cahirinus) Diabetologia 1975b 11 457 465
-
Rahier J., Goebbels R.M., Henquin J.C.Cellular composition of the human diabetic pancreas Diabetologia 1983 24 366 371
-
Robertson R.P.Type II diabetes, glucose “non-sense” and islet desensitization Diabetes 1989 38 1501 1505
-
Rubinstein A., Grosskop I., Charach G., Levtov O., Geter R., Villa Y., Goldbourt U.Lipids and lipoproteins among Ethiopian immigrants: comparison of operations Solomon and Moses Isr. J. Med. Sci 1993 29 354 359
-
Shafrir E., Diabetes in animals. Diabetes mellitus: Theory and practice Rifkin H., Porte D. Jr.Elsevier New York 1990 299 340
-
Simon C., Brandenberger G., Follenius M., Schlienger J.L.Alteration in the temporal organisation of insulin secretion in type 2 (non-insulin-dependent) diabetic patients under continuous enteral nutrition Diabetologia 1991 34 435 440
-
Stern M.P., Knapp J.A., Hazuda H.P., Haffner S.M., Patterson J.K., Mitchell B.D.Genetic and environmental determinants of type II diabetes in Mexican Americans Is there a “descending limb” to the modernization/diabetes relationship? Diabetes Care 1991 14 649 654
-
Sumburoeru D.Insulin dependent diabetes mellitus: an etiologic model Med. Hypotheses 1991 35 363 368
-
Thams P., Capito K., Hedeskov C.J., Kofod H.Phorbol-ester-induced down-regulation of protein kinase C in mouse pancreatic islets Potentiation of phase 1 and inhibition of phase 2 of glucose-induced insulin secretion. Biochem. J 1990 265 777 787
-
Tsunehara C.H., Leonetti D.L., Fujimoto W.Y.Diet of second-generation Japanese—American men with and without non-insulin-dependent diabetes Am. J. Clin. Nutr 1990 52 731 738
-
von Dorsche H.H., Krause R., Fehrmann P., Sulzmann R.The verification of neurones in the pancreas of spiny mice (Acomys cahirinus) Endokrinologie 1976 67 115 118
-
Westermark P., The pathology of the pancreas in non-insulin-dependent diabetes mellitus. Textbook of diabetes Pickup J.C., Williams G.Blackwell Scientific Publications Oxford 1991 167 171
-
Williams D.R.R., Public helath problems of diabetes and its cost to the community. Textbook of diabetes Pickup J.C., Williams G.Blackwell Scientific Publications Oxford 1991 30 34
-
Wolf B.A., Coica J.R., Turk J., Florholmen J., McDaniel M.L.Regulation of Ca2* homeostasis by islet endoplasmic reticulum and its role in insulin secretion Am. J. Physiol 1988 254 E121 136
-
Zawalich W.S., Rasmussen H.Control of insulin secretion: a model involving Ca2+, cAMP and diacylglycerol Mol. Cell. Endocrinol 1990 70 119 137
-
Zawalich W.S., Rognstad R., Pagliara A.S., Matshinsky F.M.A comparison of the utilization rates and hormone-releasing actions of glucose, mannose, and fructose in isolated pancreatic islets J. Biol. Chem 1977 252 8519 8523
-
Zawalich W.S., Zawalich K.C., Ganesan S., Calle R., Rasmussen H.Influence of staurosporine on glucose-mediated and glucose-conditioned insulin secretion Biochem. J 1991 279 807 813
-
Zimmet P., Dowse G., Bennett P.Hyperinsulinaemia is a predictor of non-insulin-dependent diabetes mellitus. Diabete Metab 1991
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THE SPINY MOUSE: IN SEARCH OF AN ANIMAL MODEL FOR PATHOGENESIS OF TYPE 2 DIABETES MELLITUS
In: Israel Journal of Ecology and EvolutionSearch for other papers by RAFAEL NESHER in
Current site
Google Scholar
PubMed
Search for other papers by EROL CERASI in
Current site
Google Scholar
PubMed
We review the data suggesting that the spiny mouse Acomys cahirinus may be a suitable model for the early stages of the development of Type 2 diabetes mellitus in man. When raised under laboratory conditions, A. cahirinus develops glucose intolerance, obesity, and varying degrees of insulin resistance. As in Type 2 diabetes, it exhibits a reduced glucose clearance rate (Kg) following an IV glucose challenge, deficient β-cell sensitivity to glucose (Km), but no change in its capacity to secrete insulin (Vmax). Its islets are well granulated with processed insulin, but, as in Type 2 diabetes, an intrinsic defect in β-cell stimulus-secretion coupling hinders the ability to meet the increasing peripheral demand for insulin caused by the developing obesity. In vitro studies with isolated islets resemble whole animal studies: a reduced early-phase insulin response to glucose (decreased Vmax), delayed and deficient late-phase response, and increased Km indicative of reduced sensitivity to glucose. We demonstrated a defective link between glycolysis, the initial step in the glucose-dependent stimulus-secretion coupling and adenylyl cyclase, a major stimulus-amplifying signaling branch, as well as a defective “readout” of the cyclic AMP signal. Additional stimulus-secretion loci are probably involved in the defective β-cell response to glucose. An integrated model for the pathogenesis of Type 2 diabetes is presented.
| All Time | Past 365 days | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 195 | 64 | 16 |
| Full Text Views | 11 | 0 | 0 |
| PDF Views & Downloads | 4 | 0 | 0 |
