Reduction of Hepatic Glycogen Synthesis and Breakdown in Patients with Agenesis of the Dorsal Pancreas

• Published in: The journal of clinical endocrinology and metabolism Vol. 87; no. 10; pp. 4678 - 4685
• Main Authors: Stingl, Harald, Schnedl, Wolfgang J., Krssak, Martin, Bernroider, Elisabeth, Bischof, Martin G., Lahousen, Theresa, Pacini, Giovanni, Roden, Michael
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01-10-2002
• Subjects: Biological and medical sciences; Blood Glucose - analysis; C-Peptide - blood; Diabetes Mellitus, Type 1 - etiology; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - metabolism; Fatty Acids, Nonesterified - blood; Female; Gastroenterology. Liver. Pancreas. Abdomen; Glucagon - blood; Gluconeogenesis; Glucose Tolerance Test; Glycogen - biosynthesis; Glycogen - metabolism; Human Growth Hormone - blood; Humans; Hydrocortisone - blood; Insulin - blood; Insulin - metabolism; Insulin Resistance; Insulin Secretion; Kinetics; Leptin - blood; Liver - metabolism; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Magnetic Resonance Spectroscopy; Male; Malformations; Medical sciences; Middle Aged; Norepinephrine - blood; Pancreas - abnormalities; Endocrinopathy; Human; Immunopathology; Agenesis; Pathophysiology; Digestive system; Family study; Glycogen; Liver; Autoimmune disease; Biosynthesis; Metabolism; Malformation; Insulin dependent diabetes; Digestive diseases; Pancreas; Comparative study; Pancreatic disease; Gluconeogenesis
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2002-020036

In a family with agenesis of the dorsal pancreas only the mother presents with insulin-dependent diabetes mellitus, whereas her sons are glucose tolerant. We examined whether metabolic defects can be detected early in this disease. Plasma glucose profiles were obtained from patients with dorsal pancreas agenesis and from matched healthy subjects. Hepatic glycogen synthesis and breakdown were determined from the time course of glycogen concentrations using noninvasive 13C nuclear magnetic resonance spectroscopy. Gluconeogenesis was calculated from the difference between glucose production (measured with d-[6,6-2H2]glucose) and glycogen breakdown. Frequently sampled iv glucose tolerance tests were performed to assess insulin secretion and sensitivity. The mean plasma glucose level was higher (12.9 ± 0.4 vs. 5.9 ± 0.1 mmol/liter), whereas the peak plasma insulin level was lower (236 vs. 397 ± 23 pmol/liter) in the diabetic mother than in her nondiabetic sons and healthy subjects. In all patients, however, glycogen synthesis and breakdown were reduced by approximately 55% (P < 0.05) and 40% (P < 0.02), respectively. Gluconeogenesis (6.8 ± 0.8 vs. 4.2 ± 0.3 μmol/kg·min; P < 0.05) and hepatic insulin clearance (6.8 ± 1.3 vs. 2.8 ± 1.0 ml/kg·min) were increased in all patients.
In conclusion, patients with complete agenesis of the dorsal pancreas exhibit marked defects in hepatic glycogen metabolism, which are present even in the nondiabetic offspring.