Hyperinsulinemia in pre-weaning diabetes (db) mice

Coleman, David L.; Hummel, Katharine P.

doi:10.1007/bf01221993

Cited by 146 publications

(99 citation statements)

References 6 publications

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“…These results agree with the findings of Coleman [2], who reported hyperinsulinemia in mdb/mdb mice older than 10 days.…”

Section: Discussionsupporting

confidence: 83%

“…On the other hand, incorporating m gene does not modify the developmental features of the diabetic syndrome [2].…”

Section: Animal Modelmentioning

confidence: 99%

“…Expression of the autosomal recessive (db)gene in homozygous (db/db) C57BL/KsJ mice results in a diabetic syndrome which evolves in stages, with each one showing different, well-defined hormonal and metabolic features [1][2][3].…”

mentioning

confidence: 99%

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Secretion and effect of somatostatin in early stages of the diabetic syndrome in C57BL/KsJ-mdb mice

et al. 1986

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Summary. In a previous study in C57BL/KsJ (mdb)mice aged 12 to 90 days, we observed alterations in the secretion of insulin and somatostatin and in the inhibitory effect of the latter upon insulin secretion. This study explores whether hormonal alterations are to be found in the very early stages of the diabetic syndrome, i.e. between ages 4 and 12 days. The results demonstrate two distinct phases in the development of the syndrome: (a) up to age 6 days, the perifused slices of pancreata of control animals present bilShasic glucose-induced patterns of insulin and somatostatin secretion, whereas the diabetic animals show a diminished first peak of insulin secretion, but a similar pattern of somatostatin secretion, to that of the control animals; Co) between ages 7 and 12 days, the pancreata of diabetic mice exhibit insulin hypersecretion in basal conditions, and an absence of the first secretion peak and insulin hypersecretion in the second phase in response to glucose stimulation. The glucose-induced pattern of somatostatin secretion presents hormonal hypersecretion in both phases. Bcell sensitivity to the inhibitory effect of somatostatin is diminished in mdb mice of the above-mentioned groups, an alteration which becomes more evident as diabetes evolves. The results show that, in very early stages of the evolution of the diabetic syndrome in C57BL/KsJ (mdb) mice, there are already alterations in insulin and somatostatin secretion patterns and in the inhibitory effect of the latter on insulin secretion. In a previous study [4] on C57BL/KsJ (db/db) mice aged 12 to 90 days, we observed: a) basal and glucosestimulated insulin hypersecretion, with absence of the first secretion peak; b) somatostatin secretion patterns showing hormonal hyper-, normo-and hyposecretion, together with altered secretion dynamics; and c) diminished B-cell sensitivity to the inhibitory effect of somatostatin, which gradually became more noticeable as animals grew older. Key words:Considering these results, we have investigated whether the above-mentioned alterations occur in very early stages (ages 4 to 12 days), or whether they are to be found during the later evolution of the diabetic syndrome in C57BL/KsJ-mdb mice. Normal homozygous and heterozygous carriers (% + + / + + and mdb/+ + genotypes) aged 4 to 12 days were used as controls and were designated as lean mice. It is necessary when using these groups as control, to know if this genotypically heterogenous population is a homogeneous one regarding insulin and somatostatin secretion. A test to determine variance equality (homoscedasticity) between the control group and the mutant group and between the control group and BALB/c mice was done. BALB/c mice were chosen because they are a genotypically population free of known deletereous mutations. Homoscedasticity did not allow the detection of an heterogeneous composition in our control group. Materials and methods Animal model Experimental models of the pancreas Incubation of pancreas slices. The technique described by Martin andBamber...

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“…These results agree with the findings of Coleman [2], who reported hyperinsulinemia in mdb/mdb mice older than 10 days.…”

Section: Discussionsupporting

confidence: 83%

“…On the other hand, incorporating m gene does not modify the developmental features of the diabetic syndrome [2].…”

Section: Animal Modelmentioning

confidence: 99%

See 1 more Smart Citation

Secretion and effect of somatostatin in early stages of the diabetic syndrome in C57BL/KsJ-mdb mice

et al. 1986

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“…The misty gene, a recessive trait, codes for a gray coat color and has a chromosomal locus very close to the db gene. It is used as a marker for determining the heterozygous (db/+) state (6). In early studies, we used both the C57BL/KsJ (++/++) black mouse and homozygous misty mice (m+/+m) for controls, as it was unclear which would be an appropriate control.…”

Section: Methodsmentioning

confidence: 99%

“…The db gene, after its identification at The Jackson Laboratory, was bred onto the C57BL/KsJ genetic strain, into which the gene for the coat color marker misty was also introduced (6). The misty gene, a recessive trait, codes for a gray coat color and has a chromosomal locus very close to the db gene.…”

Section: Methodsmentioning

confidence: 99%

Delayed Lung Maturation in the Macrosomic Offspring of Genetically Determined Diabetic (db/+) Mice1

1989

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ABSTRACT. We studied a genetically determined diabetes in pregnancy, the heterozygous diabetes (db/+) mouse. We found that fetal mice from these pregnancies are macrosomic with increased body, lung, and placenta wt, have altered organ protein, DNA and phospholipid content, and exhibit abnormal carbohydrate metabolism with increased liver and glycogen content. We further studied the effect of increased substrate availability and utilization on lung growth and maturation in (db/+) fetal mice, by measuring lung phospholipid synthesis as represented by the incorporation of the radiolabeled precursors, [3H] The increased synthesis of lung disaturated phosphatidylcholine in diabetic fetal mice may reflect the enhancement of body and lung growth in these macrosomic fetuses. Lung maturation, as represented by phosphatidylglycerol synthesis, the phosphatidylglycerol/phosphatidylinositol ratio, and morphologic indices, was abnormal in diabetic fetuses. The diabetic mouse is a useful model for studying the mechanisms resulting in enhanced growth and concomitant alterations in lung maturation in the infant of a diabetic mother. (Pediatr Res 25:173-179, 1989) Abbreviations RDS, respiratory distress syndrome PC, phosphatidylcholine SPC, disaturated phosphatidylcholine S, sphingomyelin PI, phosphatidylinositol PE, phosphatidylethanolamine PS, phosphatidylserine PG, phosphatidylglycerol Human fetal development during maternal diabetes is abnormal, frequently resulting in obese, macrosomic newborns with delayed maturation of various organ systems. Infants of diabetic mothers whose hyperglycemia is inadequately controlled late in gestation appear to have an increased risk of lung immaturity, as manifested by RDS at birth (I). Animal models in which maternal glucose intolerance and consequent fetal hyperglycemia are artificially induced have been developed to study this phenomenon (2). However, important questions concerning maternal-fetal interactions in diabetes and the consequent effects on fetal organ growth and development might be more appropriately addressed by using a model in which the diabetes is genetically determined, therefore occuning spontaneously in the mother (2).The diabetic mouse (db/db) is a well-described model of genetic diabetes transferred as an autosomal recessive trait. Homozygous (db/db) animals exhibit visible obesity in infancy with marked hyperglycemia and insulin resistance, followed later by hypoinsulinemia and profound diabetes at 3-4 mo of age (3). As the adult (db/db) mouse is infertile, heterozygous animals must be bred to produce offspring. The heterozygous female (db/ +) exhibits normal glucose tolerance except during pregnancy, when abnormal glucose tolerance, postprandial hyperglycemia and elevated Hb A 1C levels are present (4,5).We have studied the fetus of the pregnant heterozygous (db/ +) female to learn more about growth and the development during pregnancy complicated by abnormal glucose metabolism. In this report, we describe our results in characterizing abnormal fetal growth duri...

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Animal models of non‐insulin‐dependent diabetes

Shafrir

1992

Diabetes Metab. Rev.

159

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Hyperinsulinemia in pre-weaning diabetes (db) mice

Cited by 146 publications

References 6 publications

Secretion and effect of somatostatin in early stages of the diabetic syndrome in C57BL/KsJ-mdb mice

Secretion and effect of somatostatin in early stages of the diabetic syndrome in C57BL/KsJ-mdb mice

Delayed Lung Maturation in the Macrosomic Offspring of Genetically Determined Diabetic (db/+) Mice1

Animal models of non‐insulin‐dependent diabetes

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