Effect of low-level basal plus marked "pulsatile" hyperglycemia on insulin secretion in fetal sheep

Carver, Thomas D; Anderson, Susan M.; Aldoretta, Peter W.; Hay, William W.

doi:10.1152/ajpendo.1996.271.5.e865

Cited by 55 publications

(84 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These results, therefore, indicate that these islets develop a previously postulated (3,18) intrinsic defect that is, at least in part, responsible for the in vivo defect. In addition, islets isolated from the hypoglycemic fetuses failed to secrete insulin in response to leucine or lysine (although there was a near significant trend toward a response to the combination of 11 mM glucose and 5 mM arginine), indicating defective insulin secretion in response to a variety of nutrients that stimulate insulin release by different mechanisms.…”

Section: Discussionsupporting

confidence: 57%

“…Indwelling femoral arterial and venous catheters were surgically placed into the ewe and fetus by use of standard surgical and anesthetic procedures at ϳ118 dGA for T ewes and ϳ128 dGA for C ewes. Previously, we (1,3) determined that the 10-day difference in gestational age at surgery does not change basal or stimulated insulin secretion. Animals were maintained as previously described (18).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Decreased nutrient-stimulated insulin secretion in chronically hypoglycemic late-gestation fetal sheep is due to an intrinsic islet defect

Rozance¹,

Limesand²,

Hay³

2006

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Rozance, Paul J., Sean W. Limesand, and William W. Hay, Jr. Decreased nutrient-stimulated insulin secretion in chronically hypoglycemic late-gestation fetal sheep is due to an intrinsic islet defect. Am J Physiol Endocrinol Metab 291: E404 -E411, 2006. First published March 28, 2006 doi:10.1152/ajpendo.00643.2005.-We measured in vivo and in vitro nutrient-stimulated insulin secretion in late gestation fetal sheep to determine whether an intrinsic islet defect is responsible for decreased glucose-stimulated insulin secretion (GSIS) in response to chronic hypoglycemia. Control fetuses responded to both leucine and lysine infusions with increased arterial plasma insulin concentrations (average increase: 0.13 Ϯ 0.05 ng/ml leucine; 0.99 Ϯ 0.26 ng/ml lysine). In vivo lysine-stimulated insulin secretion was decreased by chronic (0.37 Ϯ 0.18 ng/ml) and acute (0.27 Ϯ 0.19 ng/ml) hypoglycemia. Leucine did not stimulate insulin secretion following acute hypoglycemia but was preserved with chronic hypoglycemia (0.12 Ϯ 0.09 ng/ml). Isolated pancreatic islets from chronically hypoglycemic fetuses had normal insulin and DNA content but decreased fractional insulin release when stimulated with glucose, leucine, arginine, or lysine. Isolated islets from control fetuses responded to all nutrients. Therefore, chronic late gestation hypoglycemia causes defective in vitro nutrient-regulated insulin secretion that is at least partly responsible for diminished in vivo GSIS. Chronic hypoglycemia is a feature of human intrauterine growth restriction (IUGR) and might lead to an islet defect that is responsible for the decreased insulin secretion patterns seen in human IUGR fetuses and low-birth-weight human infants. hypoglycemia; glucose INSULIN IS SECRETED BY THE HUMAN FETUS in response to glucose infusion, and this is attenuated in fetuses with intrauterine growth restriction (IUGR) (25). Decreased insulin secretion is likely an adaptive response by the IUGR fetus to coordinate growth with nutrient supply. This adaptive response of the developing pancreatic islets to low nutrients may explain some of the decreased ␤-cell function in small-for-gestational-age infants, most of whom had IUGR (2). Decreased ␤-cell function and development is also present in many animal models of IUGR (7,11,19,31). A main feature of human IUGR is hypoglycemia (26), which may be responsible for the decrease in pancreatic islet function in IUGR fetuses and infants. Previously, we (18) have shown that 2 wk of hypoglycemia during late gestation in fetal sheep impairs glucose-stimulated insulin secretion (GSIS) and arginine-stimulated insulin secretion. In the present study, reported herein we have used this same model to assess fetal pancreatic islet adaptation to chronic hypoglycemia to identify defects that would cause decreased insulin secretion.To achieve this, we quantified the impact of chronic and acute hypoglycemia on leucine-stimulated insulin secretion (LeuSIS) and lysine-stimulated insulin secretion (LySIS). These amino acids stimulate pancreatic ins...

show abstract

Section: Discussionsupporting

confidence: 57%

Section: Methodsmentioning

confidence: 99%

Decreased nutrient-stimulated insulin secretion in chronically hypoglycemic late-gestation fetal sheep is due to an intrinsic islet defect

Rozance¹,

Limesand²,

Hay³

2006

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

“…Moderate maternal diabetes in rats leads to an increase in fetal pancreatic insulin content, enhanced insulin secretion in response to glucose, and greater islet cell proliferation (14,25). Increased insulin secretion is observed in fetal sheep when maternal glucose levels are raised by pulsatile glucose infusion (11).…”

Section: Discussionmentioning

confidence: 99%

Maternal obesity accelerates fetal pancreatic β-cell but not α-cell development in sheep: prenatal consequences

Ford¹,

Zhang²,

Zhu³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

159

142

View full text Add to dashboard Cite

Ford SP, Zhang L, Zhu M, Miller MM, Smith DT, Hess BW, Moss GE, Nathanielsz PW, Nijland MJ. Maternal obesity accelerates fetal pancreatic ␤-cell but not ␣-cell development in sheep: prenatal consequences. Am J Physiol Regul Integr Comp Physiol 297: R835-R843, 2009. First published July 15, 2009 doi:10.1152/ajpregu.00072.2009.-Maternal obesity affects offspring weight, body composition, and organ function, increasing diabetes and metabolic syndrome risk. We determined effects of maternal obesity and a high-energy diet on fetal pancreatic development. Sixty days prior to breeding, ewes were assigned to control [100% of National Research Council (NRC) recommendations] or obesogenic (OB; 150% NRC) diets. At 75 days gestation, OB ewes exhibited elevated insulin-to-glucose ratios at rest and during a glucose tolerance test, demonstrating insulin resistance compared with control ewes. In fetal studies, ewes ate their respective diets from 60 days before to 75 days after conception when animals were euthanized under general anesthesia. OB and control ewes increased in body weight by ϳ43% and ϳ6%, respectively, from diet initiation until necropsy. Although all organs were heavier in fetuses from OB ewes, only pancreatic weight increased as a percentage of fetal weight. Blood glucose, insulin, and cortisol were elevated in OB ewes and fetuses on day 75. Insulin-positive cells per unit pancreatic area were 50% greater in fetuses from OB ewes as a result of increased ␤-cell mitoses rather than decreased programmed cell death. Lambs of OB ewes were born earlier but weighed the same as control lambs; however, their crown-to-rump length was reduced, and their fat mass was increased. We conclude that increased systemic insulin in fetuses from OB ewes results from increased glucose exposure and/or cortisol-induced accelerated fetal ␤-cell maturation and may contribute to premature ␤-cell function loss and predisposition to obesity and metabolic disease in offspring.sheep; fetal growth; pancreatic function RECENT DATA FROM THE 1999 -2002 National Health and Nutrition Examination Survey (NHANES) show that almost 65% of the adult population in the United States is overweight, defined as having a body mass index Ͼ 25 kg/m 2 , compared with 56% observed in NHANES III, conducted between 1988 and 1994 (32a). Obesity among women of reproductive age ranges from 20 to 34% (8, 10). Furthermore, Boney et al. (8) reported that by 11 years of age, children exposed to maternal obesity were at twice the risk of developing some components of the metabolic syndrome (obesity, systolic or diastolic hypertension, high triglyceride levels, low HDL levels, glucose intolerance), which suggests that obese mothers, even in the absence of gestational diabetes, may have metabolic factors that affect fetal growth and postnatal outcomes. Maternal obesity has been associated with either intrauterine growth restriction (IUGR) or large-for-gestational-age fetuses (12, 33). Both conditions are connected to offspring exhibiting altered insulin secretion and ad...

show abstract

“…Although insulin alone and in combination with cortisol did not alter LPL, we detected a 60% increase after 3 h of incubation with hyperglycemic and hyperinsulinemic medium. IDDM in pregnancy results in periods of both hyperglycemia (80) and hyperinsulinemia (80) in maternal and fetal plasma. We have shown previously that placental LPL activity is increased in MVM from IDDM mothers (27), suggesting a role for the glycemic state and insulin in regulating placental LPL.…”

Section: Discussionmentioning

confidence: 99%

Gestational and hormonal regulation of human placental lipoprotein lipase

Magnusson-Olsson

Hamark

Ericsson

et al. 2006

Journal of Lipid Research

View full text Add to dashboard Cite

The fetal demand for FFA increases as gestation proceeds, and LPL represents one potential mechanism for increasing placental lipid transport. We examined LPL activity and protein expression in first trimester and term human placenta. The LPL activity was 3-fold higher in term (n 5 7; P , 0.05) compared with first trimester (n 5 6) placentas. The LPL expression appeared lower in microvillous membrane from first trimester (n 5 2) compared with term (n 5 2) placentas. We incubated isolated placental villous fragments with a variety of effectors [GW 1929, estradiol, insulin, cortisol, epinephrine, insulin-like growth factor-1 (IGF-1), and tumor necrosis factor-a] for 1, 3, and 24 h to investigate potential regulatory mechanisms. Decreased LPL activity was observed after 24 h of incubation with estradiol (1 mg/ml), insulin, cortisol, and IGF-1 (n 5 12; P , 0.05). We observed an increase in LPL activity after 3 h of incubation with estradiol (20 ng/ml) or hyperglycemic medium plus insulin (n 5 7; P , 0.05).

show abstract

Effect of low-level basal plus marked "pulsatile" hyperglycemia on insulin secretion in fetal sheep

Cited by 55 publications

References 27 publications

Decreased nutrient-stimulated insulin secretion in chronically hypoglycemic late-gestation fetal sheep is due to an intrinsic islet defect

Decreased nutrient-stimulated insulin secretion in chronically hypoglycemic late-gestation fetal sheep is due to an intrinsic islet defect

Maternal obesity accelerates fetal pancreatic β-cell but not α-cell development in sheep: prenatal consequences

Gestational and hormonal regulation of human placental lipoprotein lipase

Contact Info

Product

Resources

About