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Lower arterial glucose concentrations in lambs with aortopulmonary shunts after an 18-hour fast
G C Beaufort-Krol1, J Takens, G B Smid
1Beatrix Children's Hospital, Division of Pediatric Cardiology, University of Groningen, The Netherlands.
Insights
Congenital heart disease with volume overloading in lambs leads to lower arterial glucose concentrations and reduced glucose production after fasting. This is linked to decreased glycogenolysis, not altered gluconeogenesis or hormonal regulation.
Area of Science:
- Pediatric Cardiology
- Metabolic Research
- Animal Models
Background:
- Hypoglycemia is observed in children with severe congestive heart failure.
- Potential causes include increased glucose utilization, decreased production, or reduced nutrient intake.
- Congenital heart disease with volume overload may also impact glucose metabolism.
Purpose of the Study:
- To investigate glucose metabolism in lambs with congenital heart disease (aortopulmonary shunt) during fasting.
- To determine if volume overloading in congenital heart disease affects glucose production and hormonal control.
Main Methods:
- Studied glucose metabolism in 9 lambs with aortopulmonary shunts and 9 controls after an 18-hour fast.
- Measured plasma hormone levels and used [U-13C]glucose to determine glucose production rate (Ra).
- Assessed gluconeogenesis via Cori cycle and fractional glucose recycling.
Main Results:
- Lambs with shunts had significantly lower arterial glucose concentrations and glucose production rates compared to controls.
- No differences were observed in hormone levels between the groups.
- Glycogenolysis was decreased in shunt lambs, while gluconeogenesis and Cori cycle activity remained similar.
Conclusions:
- Aortopulmonary shunts in lambs are associated with lower fasting arterial glucose concentrations due to reduced glucose production.
- Decreased glycogenolysis contributes to lower glucose levels in lambs with shunts.
- Hormonal regulation of glucose metabolism appears unaffected by the shunt in this model.
Abstract:
Spontaneously occurring hypoglycemia has been described in children with severe acute congestive heart failure. Hypoglycemia may be the result of an increase in glucose utilization in tissues, a decrease in glucose production, or a decrease in the dietary intake of nutrients. To determine whether hypoglycemia may also occur in congenital heart disease with volume overloading, we investigated glucose metabolism during and after an 18-hour fast in nine lambs with an aortopulmonary left-to-right shunt and nine control lambs. Plasma levels of hormones involved in the endocrine control of glucose metabolism were determined. The glucose production rate (rate of appearance [Ra]) was studied using [U-13C]glucose. Gluconeogenesis through the Cori cycle was estimated by measuring glucose 13C recycling. The arterial glucose concentration (3,409 +/- 104 v 4,338 +/- 172 micromol/L, P < .001) and Ra of glucose (16.97 +/- 0.89 v 25.49 +/- 4.28 micromol x min(-1) x kg(-1), P < .05) were lower in shunt versus control lambs. There were no differences in hormone levels between control and shunt lambs. Fractional glucose 13C recycling via the Cori cycle (6.9% +/- 2.8% v 7.1% +/- 2.5%) and gluconeogenesis from pyruvate and lactate (1.24 +/- 0.58 v 1.95 +/- 0.67 micromol x min(-1) x kg(-1)) were similar in both groups of lambs. The sum of glycogenolysis and gluconeogenesis from precursors other than pyruvate and lactate was lower in shunt versus control lambs (15.73 +/- 1.07 v 23.54 +/- 4.27 micromol x min(-1) x kg(-1), P < .05). In conclusion, after an 18-hour fast, the arterial glucose concentration is lower in lambs with aortopulmonary shunts. This lower glucose concentration is associated with a decreased glucose production rate. In shunt lambs, glycogenolysis is decreased, while there is no difference in gluconeogenesis or hormonal control.
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