Pancreatic α cell function in the fetal and newborn pig

Silver, M.; Fowden, AL; Comline, R. S.; Bloom, S. R.

doi:10.1677/joe.0.1080137

Cited by 11 publications

(17 citation statements)

References 19 publications

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“…Size and length of gestation in rodents makes it difficult to study metabolic activity in the developing foetus. In contrast, piglets are large enough to catheterize in utero (Silver et al, 1986), and one further advantage is that since the pig is a litter-bearing species several different metabolic studies can be performed using replicates within a litter.…”

Section: Litten-brown Corson and Clarkementioning

confidence: 99%

Porcine models for the metabolic syndrome, digestive and bone disorders: a general overview

Litten-Brown

Corson

Clarke

2010

Animal

147

136

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The aim of this review article is to provide an overview of the role of pigs as a biomedical model for humans. The usefulness and limitations of porcine models have been discussed in terms of metabolic, cardiovascular, digestive and bone diseases in humans. Domestic pigs and minipigs are the main categories of pigs used as biomedical models. One drawback of minipigs is that they are in short supply and expensive compared with domestic pigs, which in contrast cost more to house, feed and medicate. Different porcine breeds show different responses to the induction of specific diseases. For example, ossabaw minipigs provide a better model than Yucatan for the metabolic syndrome as they exhibit obesity, insulin resistance and hypertension, all of which are absent in the Yucatan. Similar metabolic/physiological differences exist between domestic breeds (e.g. Meishan v. Pietrain). The modern commercial (e.g. Large White) domestic pig has been the preferred model for developmental programming due to the 2-to 3-fold variation in body weight among littermates providing a natural form of foetal growth retardation not observed in ancient (e.g. Meishan) domestic breeds. Pigs have been increasingly used to study chronic ischaemia, therapeutic angiogenesis, hypertrophic cardiomyopathy and abdominal aortic aneurysm as their coronary anatomy and physiology are similar to humans. Type 1 and II diabetes can be induced in swine using dietary regimes and/or administration of streptozotocin. Pigs are a good and extensively used model for specific nutritional studies as their protein and lipid metabolism is comparable with humans, although pigs are not as sensitive to protein restriction as rodents. Neonatal and weanling pigs have been used to examine the pathophysiology and prevention/treatment of microbial-associated diseases and immune system disorders. A porcine model mimicking various degrees of prematurity in infants receiving total parenteral nutrition has been established to investigate gut development, amino acid metabolism and non-alcoholic fatty liver disease. Endoscopic therapeutic methods for upper gastrointestinal tract bleeding are being developed. Bone remodelling cycle in pigs is histologically more similar to humans than that of rats or mice, and is used to examine the relationship between menopause and osteoporosis. Work has also been conducted on dental implants in pigs to consider loading; however with caution as porcine bone remodels slightly faster than human bone. We conclude that pigs are a valuable translational model to bridge the gap between classical rodent models and humans in developing new therapies to aid human health.

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Section: Litten-brown Corson and Clarkementioning

confidence: 99%

Porcine models for the metabolic syndrome, digestive and bone disorders: a general overview

Litten-Brown

Corson

Clarke

2010

Animal

147

136

View full text Add to dashboard Cite

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“…The magnitude of this á cell response appeared to increase late in gestation in the sheep (Alexander et al 1971) but was unrelated to gestational age in the present study. The increment in plasma glucagon induced by arginine in the fetal foal was, however, positively correlated to the basal pre-infusion glucagon concentration and was greater than the increments observed in fetal sheep and pigs given the same arginine dose in late gestation (Alexander et al 1971;Silver et al 1985). These observations indicate that the number andÏor sensitivity of the á cells in the fetal equine pancreas may be greater than in other species and suggest that individual variations in these factors may determine the effectiveness of arginine in stimulating glucagon secretion in the fetal foal.…”

Section: Fastingmentioning

confidence: 73%

“…The increment in plasma glucagon at birth was probably due to the stress of labour and delivery as the newborn foals were acidotic and hyperglycaemic compared with the fetuses. Certainly, in sheep and pigs, plasma glucagon concentrations at birth are inversely related to the blood pH of the neonates (Shelley & Girard, 1981;Silver et al 1985). The pancreatic á cells of the fetal foal therefore appear to be capable of responding to the stimuli associated with delivery, although the extent to which this response is neurally or systemically mediated remains unclear.…”

Section: Fastingmentioning

confidence: 99%

“…Much less is known about á cell function in the fetus (see Fowden, 1997). Glucagon is present in fetal plasma of a number of species and its concentration is elevated during stressful conditions, such as hypoxia and anaesthesia, which lead to glucogenesis in utero (Alexander et al 1971;Chez et al 1974;Girard et al 1974;Shelley & Girard, 1981;Silver et al 1985). Glucagon has also been shown to induce hyperglycaemia and hepatic glucose production in fetuses close to term (Girard et al 1973;Devaskar et al 1984;Apatu & Barnes, 1991).…”

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confidence: 99%

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Pancreatic α Cell Function in the Fetal Foal During Late Gestation

Fowden

Forhead

Bloomfield

et al. 1999

Experimental Physiology

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summaryPlasma glucagon concentrations were measured in chronically catheterized fetal ponies and their mothers between 260 days of gestation and term ( 335 days). Fetal á cell responses to arginine and variations in fetal glycaemia were also examined during late gestation. Immunoreactive glucagon was present in fetal plasma at 260 days of gestation and its concentration in utero increased after 320 days and then again at birth. Maternal plasma glucagon concentrations were higher after 300 days than earlier in gestation but were lower than the corresponding fetal value throughout the period of gestation studied. Fetal á cells responded rapidly to intravenous arginine infusion but not to changes in the fetal glucose level induced by maternal fasting for 36 h or by intrafetal infusion of glucose. The maximal increment in fetal plasma glucagon in response to arginine occurred at the end of the 5 min infusion and was positively correlated to the basal preinfusion plasma glucagon concentrations. Fetal plasma glucagon concentrations were unaffected by either hyper-or hypoglycaemia. In contrast, maternal plasma glucagon levels were significantly increased by fasting. These observations indicate that equine pancreatic á

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“…Because glucagon and insulin are hormones that regulate hepatic P-oxidation of fatty acids, we postulated that they also might influence hepatic carnitine in the newborn period. Although elevated glucagon concentrations have been observed in newborn lambs (34), dog pups (35), and piglets within 48 h of birth (36,37), the temporal pattern through weaning had not been previously established in swine.…”

Section: Discussionmentioning

confidence: 98%

Enterohepatic Distribution of Carnitine in Developing Piglets: Relation to Glucagon and Insulin

et al. 1992

Pediatr Res

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ABSTRACT. ~Xarnitine plays a crucial role in the perinatal transition from carbohydrate to lipid-derived energy. To examine the potential contribution of assimilated dietary carnitine to the elevated hepatic concentrations in newborns, we measured carnitine concentrations in sow milk, jejunum, and liver, and in vitro jejunal carnitine transport in piglets aged 1-36 d. Hepatic and sow milk total carnitine concentrations peaked soon after birth and declined with age ( p = 0.035 and 0.026, respectively).Although jejunal total carnitine concentrations remained stable, jejunal carnitine flux was higher at 2 d of age than in older piglets. To examine the possible signals that regulate hepatic carnitine, portal enteroinsular hormones were measured by RIA. Portal glucagon ( p = 0.0006), insulin ( p = 0.0001), and g1ucagon:insulin ratio ( p = 0.037) were related to age. Portal glucagon was highest in newborns and during weaning, whereas insulin increased progressively with age; the portal g1ucagon:insulin ratio, like hepatic carnitine, peaked soon after birth and fell with age. A multiple regression analysis indicated a positive association between glucagon and hepatic carnitine and a negative one between insulin and hepatic carnitine (R = 0.802, p = 0.001). An overall pattern of elevated dietary carnitine levels and increased small intestinal absorption and hepatic accumulation of carnitine is noted in early development. The finding of a similar pattern in glucagon-to-insulin ratio suggests that both hormones may participate in the regulation of enterohepatic carnitine distribution in newborns. (Pediatr Res 32: 312-316,1992) Abbreviations PEG, polyethylene glycol SCAC, short-chain acylcarnitine ANOVA, analysis of variance NB, newborn group S, suckling group W, weaning group FW, fully weaned group plays a critical role in the metabolic transition from carbohydrate to lipid-derived energy (2, 3) because hepatic glycogen stores become rapidly depleted and endogenous gluconeogenesis is inadequate in the first 24 h of life (4, 5). As such, carnitine insufficiency has been shown to impair lipid utilization in premature newborns (6, 7). The human newborn is especially susceptible to develop carnitine insufficiency because of low levels in premature infants (8), inadequate dietary intake of carnitine (9), and insufficient endogenous synthesis (10).One marker of the switch from glucose to lipid utilization in the newborn is the increase in hepatic carnitine concentrations compared with the fetus (4). In newborn rats, the Cfold rise in hepatic carnitine has been shown to coincide with enhanced ketone production. Although the origin of hepatic carnitine in newborns has not been fully established, because endogenous synthesis is limited, dietary sources appear to be important. Human and rat milk carnitine concentrations peaked in the first few days after parturition (4, 1 1). In 5-d-old rats, the contribution of milk carnitine to heart (41%) and liver (49%) carnitine stores was substantial (12). We hypothesized that intestinal a...

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Pancreatic α cell function in the fetal and newborn pig

Cited by 11 publications

References 19 publications

Porcine models for the metabolic syndrome, digestive and bone disorders: a general overview

Porcine models for the metabolic syndrome, digestive and bone disorders: a general overview

Pancreatic α Cell Function in the Fetal Foal During Late Gestation

Enterohepatic Distribution of Carnitine in Developing Piglets: Relation to Glucagon and Insulin

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