A potential role for muscle in glucose homeostasis: in vivo kinetic studies in glycogen storage disease type 1a and fructose-1,6-bisphosphatase deficiency.
BACKGROUND
A potential role for muscle in glucose homeostasis was recently suggested based on characterization of extrahepatic and extrarenal glucose-6-phosphatase (glucose-6-phosphatase-beta). To study the role of extrahepatic tissue in glucose homeostasis during fasting glucose kinetics were studied in two patients with a deficient hepatic and renal glycogenolysis and/or gluconeogenesis.


METHODS
Endogenous glucose production (EGP), glycogenolysis (GGL), and gluconeogenesis (GNG) were quantified with stable isotopes in a patient with glycogen storage disease type 1a (GSD-1a) and a patient with fructose-1,6-bisphosphatase (FBPase) deficiency. The [6,6-(2)H(2)]glucose dilution method in combination with the deuterated water method was used during individualized fasting tests.


RESULTS
Both patients became hypoglycemic after 2.5 and 14.5 h fasting, respectively. At that time, the patient with GSD-1a had EGP 3.84 micromol/kg per min (30% of normal EGP after an overnight fast), GGL 3.09 micromol/kg per min, and GNG 0.75 micromol/kg per min. The patient with FBPase deficiency had EGP 8.53 micromol/kg per min (62% of normal EGP after an overnight fast), GGL 6.89 micromol/kg per min GGL, and GNG 1.64 micromol/kg per min.


CONCLUSIONS
EGP was severely hampered in both patients, resulting in hypoglycemia. However, despite defective hepatic and renal GNG in both disorders and defective hepatic GGL in GSD-1a, both patients were still able to produce glucose via both pathways. As all necessary enzymes of these pathways have now been functionally detected in muscle, a contribution of muscle to EGP during fasting via both GGL as well as GNG is suggested.
Huidekoper
Hidde H
HH
Department of Pediatrics Academic Medical Center, University Hospital of Amsterdam, The Netherlands.
Visser
Gepke
G
Ackermans
Mariëtte T
MT
Sauerwein
Hans P
HP
Wijburg
Frits A
FA
D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D015319:Fructose-1,6-Diphosphatase Deficiency / Q000235:genetics*; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism*; D005953:Glycogen Storage Disease Type I / Q000235:genetics*; D050261:Glycogenolysis; D006706:Homeostasis; D006801:Humans; D007003:Hypoglycemia / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000378:metabolism*
D001786:Blood Glucose; D005947:Glucose