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| Hepatic metabolism in Diabetes |
| Manuela Carvalheiro (HUC), John G. Jones (CNC) |
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Noninvasive measurement of hepatic glycogen kinetics in Type 1 diabetics:
Synthesis of liver glycogen from dietary carbohydrate during feeding and its hydrolysis to glucose during fasting plays a key role in maintaining normal blood glucose levels during the daily feeding-fasting cycle. Liver glycogen metabolism is defective in many Type-1 diabetes (T1D) patients therefore its improvement is an important milestone for achieving good glycemic control. Evaluation of glycogen kinetics in humans presently limited to a few specialized clinical magnetic resonance (MR) research centers. The MR method directly observes liver glycogen levels and is therefore considered to be the “gold standard” measurement.
We developed a simple and noninvasive measurement of liver glycogen dynamics using deuterated water as a metabolic tracer. This measurement is relatively inexpensive and can be performed in any hospital. Our pilot studies revealed significant differences in hepatic glycogen metabolism between T1D patients and healthy controls that are consistent with those described using “gold standard” clinical MR measurements.
Hepatic glucose metabolism in renal transplant patients treated with cyclosporine (CsA):
In an era in which successful renal transplantation is offered to a growing number of patients with end-stage renal disease, there is increasing concern about complications that develop after the transplantation of a functioning allograft in particular post-transplant diabetes mellitus (PTDM). It is recognized that immunosuppressant therapy plays an important role in PTDM development since these medications exhibit a wide spectrum of diabetogenic effects. As the liver plays a principal role in glucose homeostasis it is vital to elucidate how CsA affects hepatic glucose metabolism. Using stable isotope tracers to study the effect of CsA in hepatic glucose metabolism we hope for a better understanding of the underlying mechanisms of PTDM associated with CsA. |
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| PUBLICATIONS |
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| Jones, J.G., Fagulha,A., Barosa, C., Bastos, M., Barros, L., Baptista, C., Caldeira M., and Carvalheiro M. 2006. Noninvasive analysis of hepatic glycogen kinetics before and after breakfast with deuterated water and acetaminophen. Diabetes, 55, 2294-2300. |
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| Jones, J.G., Barosa, C, Gomes, F., Mendes, A.C., Delgado, T.C., Diogo, L., Garcia, P., Bastos, M., Barros, L., Fagulha, A., Baptista, C., Carvalheiro, M. and Caldeira, M.M. 2006. NMR derivatives for quantification of 2H and 13C-enrichment of human glucuronide from metabolic tracers. J. Carbohydrate Chem. 25, 203-217. |
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| Ribeiro, A., Caldeira, M.M., Carvalheiro, M., Bastos, M., Baptista, C., Fagulha, A., Barros, L., Barosa, C. And Jones, J.G. 2005. A simple measurement of gluconeogenesis by direct 2H NMR analysis of menthol glucuronide enrichment from 2H2O. Magn. Res. Med. 54, 429-434. |
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Funding
Juvenile Diabetes Research Foundation International: JDRFI 5-2004-306; JDRF1 1-2006-74
FCT: POCTI/QUI/55603/2004; POCTI/SAU~OSM/65140/2006 |
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