Glucose Utilization in Relation to Insulin Secretion in NZO and C57B1 Mouse Islets*

Larkins, R. G.; Simeonova, Lora; Veroni, M.

doi:10.1210/endo-107-5-1634

Cited by 12 publications

(11 citation statements)

References 24 publications

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“…In this regard, it also resembles the human condition. Previous studies on the NZO mouse have shown evidence for insulin resistance in skeletal muscle (17,21,22), white adipose tissue (17,21,23,24), and the liver (25) as well as defects in glucose-stimulated insulin secretion (15,16,(26)(27)(28)(29).…”

Section: Discussionmentioning

confidence: 99%

Evolution of Insulin Resistance in New Zealand Obese Mice

1991

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The etiology of non-insulin-dependent diabetes mellitus (NIDDM) is not known. Hyperglycemia is due to increased hepatic glucose production (HGP), decreased glucose uptake, and impaired insulin secretion. It is unknown if these defects are coinherited or if one precedes and causes the others. The aim of this study was to determine the earliest defects in the evolution of the syndrome in the New Zealand obese (NZO) mouse, a polygenic model of NIDDM. NZO and control NZC mice were studied at 4-5 and 20 wk of age. Glucose turnover and glucose uptake in individual tissues were measured basally and during a hyperinsulinemic clamp. First-phase insulin secretion was measured after an intravenous glucose load. HGP was higher in the NZO mice both basally and during the clamp at both ages. At 4-5 wk of age, there was evidence of insulin insensitivity in brown adipose tissue, soleus, diaphragm, red quadriceps, and red gastrocnemius but not in heart, white quadriceps, and white gastrocnemius. In 20-wk-old mice, insulin responsiveness was decreased in white and brown adipose tissue and soleus muscle but not in heart, diaphragm, red and white quadriceps, and red and white gastrocnemius. First-phase insulin secretion (percentage rise above basal) 3 min after the glucose bolus was impaired in NZO mice at both ages. We conclude that hepatic glucose overproduction, brown adipose tissue and skeletal muscle insulin resistance, and impaired first-phase insulin secretion are all early abnormalities in the NZO mouse.

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Section: Discussionmentioning

confidence: 99%

Evolution of Insulin Resistance in New Zealand Obese Mice

1991

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“…Glucose utilization was determined by measuring the formation of 3 (19,20). Islets were preincubated in KRB (as in the insulin secretion studies) for 30 min before groups of 10 islets were incubated in 40 l fresh KRB containing 20 mm glucose and 2 Ci …”

Section: Glucose Utilizationmentioning

confidence: 99%

Comparison of Insulin Secretory Function in Two Mouse Models with Different Susceptibility to β-Cell Failure

et al. 2002

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Type 2 diabetes is characterized by a susceptibility to beta-cell failure. However, subjects at risk of developing type 2 diabetes, such as those with obesity or a family history of diabetes, have been shown to display hyperinsulinemia. Although this hyperinsulinemia may be an adaptive response to insulin resistance, the possibility that insulin hypersecretion may be a primary defect has not been thoroughly investigated. The DBA/2 mouse is a model of pancreatic islet susceptibility. Unlike the resistant C57BL/6 mouse strain, the DBA/2 mouse islet fails when stressed with insulin resistance or when exposed to chronic high glucose concentrations. The aim of this study was to compare insulin secretory function in the DBA/2 and C57BL/6 strains in the absence of insulin resistance or high glucose. Insulin secretion was assessed in vivo using the iv glucose tolerance test and in vitro using isolated islets in static incubations. It was shown that DBA/2 mice hypersecreted insulin in vivo, compared with C57BL/6 mice, at 1 d and at 4 and 10 wk of age. This hypersecretion was not attributable to insulin resistance (as assessed by the insulin tolerance test) or increased parasympathetic nervous system outflow. Insulin hypersecretion was also demonstrated in vitro. This was associated with higher glycolysis and glucose oxidation, and elevated activity (but not protein levels) of islet glucokinase and hexokinase. Furthermore, GLUT2 protein levels were higher, which may explain an increase in glucokinase activity in DBA/2 mouse islets. In summary, the DBA/2 mouse, a model of islet failure, has increased glucose-mediated insulin secretion from a very early age, which is associated with an increase in glucose utilization. Further studies will determine whether there is a link between insulin hypersecretion and subsequent beta-cell failure.

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“…This rodent has the typical hyperinsulinism and insulin resistance associated with obesity; blood glucose is mildly elevated, if at all. 60 Uniquely, it has a high incidence of autoimmune disorders, including circulating antibodies against tissue insulin receptors. 61 Glomerular nephritis from immune complexes is common.…”

Section: Obese Modelsmentioning

confidence: 99%

Metabolic and Underlying Causes of Diabetes Mellitus

Grodsky¹,

Anderson²,

Coleman³

et al. 1982

Diabetes

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It is emphasized that animal models should be used to study specific genotypic or phenotypic expressions associated with diabetes rather than assuming a single animal model can reflect diverse forms of the human disease. Diabetic and normal animals are reviewed on the basis of their usefulness as models of genetic, viral, and chemically induced diabetes, including the often associated immune phenomena. Characteristics of spontaneously diabetic animals with and without obesity are also described with an emphasis on both genetics and metabolic derangements.Recommendations for future animal experimentation include: more longitudinal studies evaluating the role of sex, prenatal environment, diet, and viral or chemical attack on B-cell function; characterization of the immune phenomena associated with B-cell lesions (and insulitis) in diabetic and immunologically incompetent lines; clarification of relationships between obesity and islet-cell function with emphasis on the role of fuel metabolism, vitamins, and minerals; and, finally, the development of new models with specific genetic aberrations placed in normal or diabetic lines. DIABETES 31 (Suppl. 1):45-53, 1982.

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Glucose Utilization in Relation to Insulin Secretion in NZO and C57B1 Mouse Islets*

Cited by 12 publications

References 24 publications

Evolution of Insulin Resistance in New Zealand Obese Mice

Evolution of Insulin Resistance in New Zealand Obese Mice

Comparison of Insulin Secretory Function in Two Mouse Models with Different Susceptibility to β-Cell Failure

Metabolic and Underlying Causes of Diabetes Mellitus

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