Maturation of Early-Phase Insulin Release in the Neonatal Lamb

Philipps, Anthony F; Dubin, Joseph W.; Raye, John R.

doi:10.1159/000241441

Cited by 13 publications

(4 citation statements)

References 22 publications

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“…Compared with adult plasma, fetal plasma has been found to contain little proinsulin during late gestation, although both intact and split proinsulin are present in cord plasma from human infants at birth (Godfrey et al 1996). In sheep, the pancreatic cells become progressively more responsive towards term and are very sensitive to changes in glycaemia in the immediate neonatal period (Phillips et al 1981, Aldoretta et al 1998. Similarly, in horses, there are increases in pancreatic cell sensitivity to glucose during late gestation and, again, between birth and 7 days of postnatal age (Fowden et al 1980(Fowden et al , 1982.…”

Section: Introductionmentioning

confidence: 99%

Development of insulin and proinsulin secretion in newborn pony foals

Holdstock

Allen²,

Bloomfield³

et al. 2004

Journal of Endocrinology

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At birth, the endocrine pancreas must assume a glucoregulatory role if the neonate is to survive the transition from parenteral to enteral nutrition. In species like the horse, neonatal hypoglycaemia is common, which suggests that the glucoregulatory mechanisms are not always fully competent at birth. Hence, this study examined pancreatic cell function in newborn foals during nutritional adaptation over the first 10 days post partum. Over a 48 h period at three time intervals after birth (days 1-2, 5-6 and 9-10 post partum), the cell responses to suckling and to intravenous administration of glucose, arginine and saline were measured in seven normal pony foals. Basal plasma concentrations of proinsulin, but not insulin or glucose, increased significantly between days 1 and 10. Suckling caused a gradual increase in plasma glucose, which was accompanied by a significant increase in plasma insulin concentrations 15 min after the onset of suckling on days 5 and 9, but not day 1. There was no significant change in plasma proinsulin concentrations in response to suckling at any age. At all ages studied, glucose and arginine administration stimulated an increase in the plasma concentrations of insulin and proinsulin; these cell responses did not change significantly with postnatal age. The insulin responses to glucose were significantly greater than those of arginine at each time period. Glucose clearance was significantly slower on day 1 than subsequently. Proinsulin and glucose, but not insulin, concentrations decreased significantly after saline administration at all three ages. At each time period, there was a significant positive relationship between the plasma insulin and proinsulin concentrations, the slope of which was significantly shallower on days 1-2 than subsequently. These results show that equine cells are responsive to glucose and arginine and release both insulin and proinsulin during the immediate postnatal period. They also suggest that newborn foals may be insulin resistant on the first day after birth.

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Section: Introductionmentioning

confidence: 99%

Development of insulin and proinsulin secretion in newborn pony foals

Holdstock

Allen²,

Bloomfield³

et al. 2004

Journal of Endocrinology

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“…In addition to birth weight as a predictor for increased risk of diabetes, neonatal events that impact growth trajectory have also been shown to influence metabolic outcomes (43). There is a paucity of information on the transition of IUGR infants into childhood because insulin action and secretion continue to develop and mature with age (23,31,46). To our knowledge, only a few studies in IUGR infants have investigated the early transition into neonatal life (24 to 72 h).…”

mentioning

confidence: 99%

Enhanced insulin secretion and insulin sensitivity in young lambs with placental insufficiency-induced intrauterine growth restriction

Camacho

Chen

Hay

et al. 2017

American Journal of Physiology-Regulatory, Integrative and Comp

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Intrauterine growth restriction (IUGR) is associated with persistent metabolic complications, but information is limited for IUGR infants. We determined glucose-stimulated insulin secretion (GSIS) and insulin sensitivity in young lambs with placental insufficiency-induced IUGR. Lambs with hyperthermia-induced IUGR ( = 7) were compared with control lambs ( = 8). GSIS was measured at 8 ± 1 days of age, and at 15 ± 1 days, body weight-specific glucose utilization rates were measured with radiolabeled d-glucose during a hyperinsulinemic-euglycemic clamp (HEC). IUGR lambs weighed 23% less ( < 0.05) than controls at birth. Fasting plasma glucose and insulin concentrations were not different between IUGR and controls for either study. First-phase insulin secretion was enhanced 2.3-fold in IUGR lambs compared with controls. However, second-phase insulin concentrations, glucose-potentiated arginine-stimulated insulin secretion, and β-cell mass were not different, indicating that IUGR β-cells have an intrinsic enhancement in acute GSIS. Compared with controls, IUGR lambs had higher body weight-specific glucose utilization rates and greater insulin sensitivity at fasting (1.6-fold) and hyperinsulinemic periods (2.4-fold). Improved insulin sensitivity for glucose utilization was not due to differences in skeletal muscle insulin receptor and glucose transporters 1 and 4 concentrations. Plasma lactate concentrations during HEC were elevated in IUGR lambs compared with controls, but no differences were found for glycogen content or citrate synthase activity in liver and muscle. Greater insulin sensitivity for glucose utilization and enhanced acute GSIS in young lambs are predicted from fetal studies but may promote conditions that exaggerate glucose disposal and lead to episodes of hypoglycemia in IUGR infants.

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“…Mean plasma glucose concentration stabilized after 3-5 days and averaged 372 ± 24 mg/dl, considerably above the value of 98 ± 8 mg/dl observed for non-STZ-treated lambs. 15 Despite overt hyperglycemia, plasma insulin concentrations remained low, 21 ± 10 |xU/ml. No changes in plasma insulin concentration were observed in the three lambs after intravenous tolbutamide challenge.…”

Section: Resultsmentioning

confidence: 98%

“…Plasma glucose concentration rises dramatically after birth in the lamb, 15 presumably because of complex factors including stress, increases in hepatic glucose production, and milk feeding, with resultant increases in gut hormone secretion. An exaggeration of these responses might be anticipated if the counterregulatory effects of enhanced insulin release were not present.…”

Section: Discussionmentioning

confidence: 99%

Effects of Fetal Insulin Secretory Deficiency on Metabolism in Fetal Lamb

et al. 1986

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Fetal insulin secretion may be of importance in determining both fetal metabolic rate and glucose homeostasis in the resting state. To investigate this question, streptozocin (STZ) was injected into 10 late-gestation fetal lambs, and the effects of STZ on fetal pancreatic insulin storage and secretion, fetal metabolic rate, and umbilical glucose uptake were then studied. Fetal STZ injection caused a relative fetal hyperglycemia by 24 h after injection. Fetal hyperglycemia reached a maximum by 72 h and persisted for at least 10 days after injection. Neonates delivered after fetal injection were frankly diabetic. Fetal STZ injection was associated with complete suppression of both glucose- and tolbutamide-stimulated insulin release, although no changes in peripheral insulin concentration were observed when compared with controls. Fetal pancreatic insulin content was only 13% of that expected on the basis of gestational age. In a subgroup of 7 STZ-treated fetal lambs, fetal hyperglycemia was related to decrements in umbilical venoarterial difference of glucose, umbilical glucose uptake, and glucose-O2 quotient. No changes in maternal glucose homeostasis or in fetal O2 consumption were noted. The data suggest that deficient fetal insulin storage and secretion are associated with a decrement in exogenous fetal glucose entry but not in fetal metabolic rate. Whether the observed fetal changes relate to enhanced endogenous fetal glucose production with a passive decrease in maternofetal glucose transfer or are simply due to a decrease in overall fetal glucose utilization is not known. It is speculated that a quantitative decrease in pancreatic insulin secretion is responsible for the observed changes.

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Maturation of Early-Phase Insulin Release in the Neonatal Lamb

Cited by 13 publications

References 22 publications

Development of insulin and proinsulin secretion in newborn pony foals

Development of insulin and proinsulin secretion in newborn pony foals

Enhanced insulin secretion and insulin sensitivity in young lambs with placental insufficiency-induced intrauterine growth restriction

Effects of Fetal Insulin Secretory Deficiency on Metabolism in Fetal Lamb

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