Age-Dependent Onset of Insulin Resistance in Insulin-Resistant Mice
| Autor: | Kanami Ogura, Kasumi Arisawa, Yoshiyuki Kagawa, Naohito Ide, Toshio Maeda |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty Phenylalanine medicine.medical_treatment Pharmaceutical Science Adipose tissue Mice Inbred Strains Nateglinide Insulin resistance Cyclohexanes Internal medicine Insulin receptor substrate Glucose Intolerance medicine Animals Hypoglycemic Agents Insulin Obesity RNA Messenger Receptor Pharmacology Glucose tolerance test medicine.diagnostic_test biology business.industry Age Factors General Medicine medicine.disease Receptor Insulin Insulin receptor Glucose Endocrinology Adipose Tissue Insulin Receptor Substrate Proteins biology.protein Insulin Resistance business medicine.drug |
| Zdroj: | Biological & Pharmaceutical Bulletin. 38:1925-1934 |
| ISSN: | 1347-5215 0918-6158 |
| DOI: | 10.1248/bpb.b15-00602 |
| Popis: | We have previously isolated spontaneous insulin-resistant mice (ddY-H) and non-insulin-resistant mice (ddY-L) from ddY mice. In the present study, age-dependent onset of insulin resistance in obese ddY-H mice was investigated by comparing with lean ddY-L mice. In ddY-H mice fed a standard diet, an increase in elevation of glucose-stimulated plasma insulin level, glucose intolerance in an intraperitoneal glucose tolerance test, and a reduction of hypoglycemic action of insulin were found at 9 weeks of age, but not at 6 weeks of age. When ddY-H mice were administered nateglinide, a greater elevation of plasma insulin level and a less decrease of serum glucose level were observed at 9 weeks of age. These changes developed progressively with age. These findings suggest that insulin resistance is induced at 9 weeks of age. The age-related change in insulin resistance was correlated with reductions in mRNA expression and protein content of the insulin receptor (InsR), and insulin receptor substrate (IRS)-1 and IRS-2 in the epididymal adipose tissue. On the other hand, in the liver, mRNA expression of InsR and IRS-1 did not change at any age, although that of the IRS-2 was reduced. Thus, in ddY-H mice, insulin resistance and glucose-stimulated hyper-secretion of insulin are induced at 9 weeks of age and are reciprocally affected, resulting in progression to a more severe state at an older age. Insulin resistance may be attributed, at least in part, to the decreases in the mRNA expressions and proteins of InsR, IRS-1 and IRS-2 in adipose tissue. |
| Databáze: | OpenAIRE |
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