The diabetic intrauterine milieu has a long-lasting effect on insulin secretion by B cells and on insulin uptake by target tissues

Aerts, Luc; Sodoyez-Goffaux, F; Sodoyez, J. C.; Malaisse, Willy; Assche, F Van

doi:10.1016/0002-9378(88)90465-6

Cited by 93 publications

(48 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The present results indicate that, using the definitions of Kahn [8], the peripheral tissues of SDF-rats are less sensitive (decreased half-maximal effect) to insulin, thus confirming our previous results of 123I-insulin captation experiments [5]. On a weight basis, skeletal muscle is the most important glucose-utilizing tissue [11].…”

Section: Discussionsupporting

confidence: 90%

“…glucose infusion, maintained glucose levels within the control range in the presence of increased insulin levels [4]. Moreover, in vivo 123I-insulin captation studies in these rats demonstrated an elevated renal clearance of insulin, which also suggests a decreased uptake of insulin by peripheral tissues [5]. In the same study, we found that islets of Langerhans were more sensitive to glucose in vitro in SDF-rats than in control rats [5]; it was then postulated that this hypersecretion of insulin was the consequence of an insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

“…The adult offspring of severely hyperglycaemic pregnant rats (SDF-rats) have a normal pancreas on histology and normal serum glucose and insulin concentrations in basal conditions, but their glucose tolerance is clearly impaired [3,4]. Data from an in vivo 123I-insulin captation study would suggest an insulin resistance in SDF-rats [5]. In this study, we used the euglycaemic hyperinsulinaemic clamp method [6,7] to characterize and quantitate the postulated insulin resistance in SDF-rats.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Evidence for an insulin resistance in the adult offspring of pregnant streptozotocin-diabetic rats

1991

Self Cite

View full text Add to dashboard Cite

Summary.Our previous work has suggested the presence of an insulin resistance in the adult offspring of streptozotocindiabetic pregnant rats. In this study we used the euglycaemic hyperinsulinaemic clamp technique with an isotope-dilution method to define and quantify this postulated insulin resistance in adult offspring of streptozotocin-diabetic rats. Under basal conditions, these rats had a lower body weight than control rats, but their glucose and insulin concentrations were normal. During the hyperinsulinaemic clamp, the steady-state glucose infusion rate was significantly lower in the offspring of streptozotocin-diabetic rats than in both ageand weight-matched controls, indicating insulin resistance. Basal peripheral tissue glucose utilization was normal in the offspring of streptozotocin-diabetic rats, but the dose-response curve was shifted to the right: insulin concentrations causing half-maximal stimulation of glucose utilization were increased by about 60% in the offspring of diabetic rats; the maximal stimulation of glucose utilization, however, was unaltered. Basal hepatic glucose production was normal, but again, half-maximal suppression of glucose production occurred at insulin concentrations 50% higher than in controt rats; in addition, the maximal suppression of glucose production was significantly decreased, even at insulin concentrations of 5700 btU/ml. These data are evidence for an insulin resistance in the adult offspring of streptozotocin-diabetic rats, characterized by: (1) a decreased insulin sensitivity by peripheral glucose-utilizing tissues, and, (2) a decreased sensitivity and responsiveness of the liver. Key words:Insulin resistance, euglycaemic hyperinsulinaemic clamp, offspring of streptozotocin-diabetic rats.Metabolic changes in the pregnant streptozotocindiabetic rat have been shown to affect fetal development and fetal glucose homeostasis [1, 21. A severe hyperglycaemia ( > 20 mmol/1) in the maternal rat results in hyperglycaemia and hypoinsulinaemia of their fetuses. On histology and electronmicroscopy, we found evidence of islet hypertrophy, Beta-cell hyperplasia and Beta-cell degranulation in these fetuses: a 'Beta-cell exhaustion phenomenon' is probably the cause of decreased insulin levels in fetal serum [1,2]. Malnutrition of the newborn rats by their mothers, causes frequent postnatal death and subnormal glucose and insulin levels in the survivors until weaning [1,3]. Body weight in the offspring of severely hyperglycaemic rats is significantly lower than normal from day 20 of gestation and it remains significantly lower during postnatal life: during the lactation period and after weaning [1][2][3]. The adult offspring of severely hyperglycaemic pregnant rats (SDF-rats) have a normal pancreas on histology and normal serum glucose and insulin concentrations in basal conditions, but their glucose tolerance is clearly impaired [3,4]. Data from an in vivo 123I-insulin captation study would suggest an insulin resistance in SDF-rats [5]. In this study, we used the euglycaemic ...

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Evidence for an insulin resistance in the adult offspring of pregnant streptozotocin-diabetic rats

1991

Self Cite

View full text Add to dashboard Cite

show abstract

“…Furthermore, studies in rats injected with streptozotocin or infused with glucose have demonstrated that hyperglycemia in the mother during the pregnancy leads to impairment of glucose tolerance, impaired insulin secretion, and increased insulin resistance in the adult offspring (19)(20)(21)(22)(23)(24)(25). Thus, our findings in the Pima Indians are consistent with the animal studies and show a distinct effect of the intrauterine diabetic environment on the risk of diabetes and obesity in offspring.…”

Section: Discussionsupporting

confidence: 88%

Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships.

Dabelea

Hanson²,

Lindsay³

et al. 2000

Diabetes

1,150

741

View full text Add to dashboard Cite

Intrauterine exposure to diabetes is associated with an excess of diabetes and obesity in the offspring, but the effects of intrauterine exposure are confounded by genetic factors. To determine the role of the intrauterine diabetic environment per se, the prevalence of diabetes and the mean BMI were compared in siblings born before and after their mother was recognized as having diabetes. Nuclear families in which at least one sibling was born before and one after the mother was diagnosed with type 2 diabetes were selected. Consequently, the siblings born before and after differed in their exposure to diabetes in utero. A total of 58 siblings from 19 families in which at least one sibling had diabetes were examined at similar ages (within 3 years). The risk of diabetes was significantly higher in siblings born after the mother developed diabetes than in those born before the mother's diagnosis of diabetes (odds ratio 3.7, P = 0.02). In 52 families, among 183 siblings without diabetes, the mean BMI was 2.6 kg/m 2 higher in offspring of diabetic than in offspring of nondiabetic pregnancies (P = 0.003). In contrast, there were no significant differences in risk of diabetes or BMI between offspring born before and after the father was diagnosed with diabetes. Intrauterine exposure to diabetes per se conveys a high risk for the development of diabetes and obesity in offspring in excess of risk attributable to genetic factors alone. Diabetes 49:2208-2211, 2000 T ype 2 diabetes has strong genetic and environmental risk factors. Previous studies have shown greater transmission of type 2 diabetes to offspring from mothers than from fathers (1-3), and a significantly higher prevalence of diabetes in offspring of women with diabetes during pregnancy than in offspring of nondiabetic and prediabetic women (2). Intrauterine exposure to diabetes is also associated with a higher prevalence of impaired glucose tolerance in adolescence (4) and with an excess of obesity, especially during the first 20 years of life (5-7). Nevertheless, the effects of intrauterine exposure to diabetes may be confounded by genetic factors. For example, women who develop diabetes at an earlier age might carry more diabetes-susceptibility genes than those who develop diabetes later. Hence, they might transmit greater genetic susceptibility to their offspring.The Pima Indians of Arizona have the world's highest incidence and prevalence of type 2 diabetes (8,9). Both genetic and environmental risk factors contribute to the high rate of diabetes in the Pimas. In Pima Indian children aged 5-19 years, the strongest single risk factor for type 2 diabetes was exposure to diabetes in utero (10). To determine the role of intrauterine diabetic environment, which is in addition to genetic transmission of susceptibility, a sibship study was designed to compare the prevalence of type 2 diabetes and the BMI in Pima Indian siblings born before and after their mother was diagnosed with type 2 diabetes. RESEARCH DESIGN AND METHODSData were taken from the longitudinal ...

show abstract

“…6B) [52]. The observation that the offspring of rats made mildly diabetic during preg-nancy have reduced insulin secretion in response to glucose [70] has led to the hypothesis that intrauterine exposure to hyperglycaemia during critical periods of fetal development`programs' the developing pancreas in a way that negatively affects subsequent insulin secretory function.…”

Section: Determinants Of First-phase Insulin Secretionmentioning

confidence: 99%

The role of impaired early insulin secretion in the pathogenesis of Type II diabetes mellitus

2001

View full text Add to dashboard Cite

Normal glucose tolerance is maintained by a precise balance between insulin secretion from pancreatic beta cells and insulin action on sensitive tissues, principally muscle, adipose tissue and liver [1,2]. Patients with Type II (non-insulin-dependent) diabetes mellitus manifest impairments in insulin secretion and insulin action and an increased rate of endogenous glucose production [1±3]. The relative importance of these abnormalities in the pathogenesis of the disease has been debated for many years. It is now generally accepted that abnormalities in insulin secretion and insulin action contribute to the development of Type II diabetes, whereas the increase in endogenous glucose production is a later phenomenon. Insulin secretory dysfunction in Type II diabetes is both quantitative and qualitative [3±4]. In addition to a relative impairment in the amount of insulin released, the pattern of insulin secretion is abnormal. In this review, we focus on the critical role of impaired early insulin secretion in the pathogenesis of Type II diabetes.Current understanding of the pathophysiology of Type II diabetes is based on the contributions of many laboratories working with different populations around the world. Since 1982, the National Institutes of Health has conducted a longitudinal study of the metabolic predictors of Type II diabetes in the Pima Indians of Arizona [5], a population uniquely suited for such studies because of their extraordinarily high Diabetologia (2001) AbstractPatients with Type II (non-insulin-dependent) diabetes mellitus manifest abnormalities in insulin action and insulin secretion. It is widely accepted that insulin resistance is an early finding, evident before the onset of hyperglycaemia and predictive of the subsequent development of diabetes. Whether abnormalities in insulin secretion also precede and predict diabetes has been debated. However, recent studies clearly indicate that early insulin secretion plays a critical role in maintaining normal glucose homeostasis. Crosssectional analyses show that acute insulin secretory responses (AIR) to intravenous glucose are lower in subjects with impaired glucose tolerance and those at high risk for developing diabetes. Prospectively, a low AIR predicts the development of diabetes in several populations. In longitudinal studies, AIR declines dramatically as patients progress from normal to impaired glucose tolerance and ultimately to diabetes. Early insulin secretion is important for the rapid and efficient suppression of endogenous glucose production after a meal. Thus, loss of early insulin secretion initially leads to post-prandial hyperglycaemia which, as the disease progresses, worsens to clinical hyperglycaemia. Strategies that enhance early insulin secretion improve glucose tolerance and represent a novel and more physiologic approach to improving glycaemic control in patients with Type II diabetes mellitus. [Diabetologia (2001) 44: 929±945]

show abstract

The diabetic intrauterine milieu has a long-lasting effect on insulin secretion by B cells and on insulin uptake by target tissues

Cited by 93 publications

References 13 publications

Evidence for an insulin resistance in the adult offspring of pregnant streptozotocin-diabetic rats

Evidence for an insulin resistance in the adult offspring of pregnant streptozotocin-diabetic rats

Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships.

The role of impaired early insulin secretion in the pathogenesis of Type II diabetes mellitus

Contact Info

Product

Resources

About