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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
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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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| Insgesamt | Letzte 365 Tage | In den letzten 30 Tagen | |
|---|---|---|---|
| Aufrufe von Kurzbeschreibungen | 198 | 67 | 17 |
| Gesamttextansichten | 11 | 0 | 0 |
| PDF-Downloads | 4 | 0 | 0 |
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.
| Insgesamt | Letzte 365 Tage | In den letzten 30 Tagen | |
|---|---|---|---|
| Aufrufe von Kurzbeschreibungen | 198 | 67 | 17 |
| Gesamttextansichten | 11 | 0 | 0 |
| PDF-Downloads | 4 | 0 | 0 |
