Ph Schneiter

A non- invasive assessment of hepatic glycogen kinetics and post- absorptive gluconeogenesis in man

SummaryA novel approach to the study of hepatic glycogen kinetics and fractional gluconeogenesis in vivo is described. Ten healthy female subjects were fed an iso-caloric diet containing 55 % carbohydrate energy with a 13C abundance of 1.083 atom percent for a 3-day baseline period; then, a diet of similar composition, but providing carbohydrate with a 13C abundance of 1.093 atom percent was started and continued for 5 days. Resting respiratory gas exchanges, urinary nitrogen excretion, breath 13CO2 and plasma 13C glucose were measured every morning in the fasting state. The enrichment in 13C of hepatic glycogen was calculated from these measured data. 13C glycogen enrichment increased after switching to a 13C enriched carbohydrate diet, and was identical to the 13C enrichment of dietary carbohydrates after 3 days. The time required to renew 50 % of hepatic glycogen, as determined from the kinetics of 13C glycogen enrichment, was 18.9 ± 3.6 h. Fractional gluconeogenesis, as determined from the difference between the enrichments of glucose oxidized originating from hepatic glycogen and plasma glucose 13C was 50.8 ± 5.3%. This non-invasive method will allow the study of hepatic glycogen metabolism in insulin-resistant patients.

Endogenous glucose production, gluconeogenesis and liver glycogen concentration in obese non-diabetic patients

Summary Resting, post-absorptive endogenous glucose production (EGP), fractional gluconeogenesis and liver glycogen concentration were assessed in 6 lean and 5 obese non-diabetic subjects undergoing elective abdominal surgery. During the 2 days preceding these measurements, 0.3 g/day U-13C glucose had been added to their usual diet to label their endogenous glycogen stores. On the morning of day 3, EGP was measured with 6,6-2H glucose. Their endogenous 13C glycogen enrichment was calculated from 13CO2 and respiratory gas exchanges. Fractional gluconeogenesis was assessed as 1-(13C glucose/13C glycogen) · 100. EGP was similar in lean subjects (113 ± 5 mg/min) and in obese subjects (111 ± 6). Fractional gluconeogenesis was higher in obese (59 ± 10 %) than in lean subjects (29 ± 8 %). However, overall EGP remained constant due to a decrease in glycogenolysis. Since an increased gluconeogenesis and a decreased glycogenolysis may both contribute to increase liver glycogen concentration in obesity, hepatic glycogen concentrations were assessed in hepatic needle biopsies obtained during surgery. Hepatic glycogen concentrations were increased in obese patients (515 ± 38 mg/g protein) compared to lean subjects (308 ± 58, p < 0.05). It is concluded that in obese patients: a) fractional gluconeogenesis is increased; b) overall EGP is unchanged due to a proportional inhibition of glycogenolysis; c) liver glycogen concentration is increased. [Diabetologia (1997) 40: 463–468]

Energy expenditure, physical activity and body-weight control

Regular physical exercise and endurance training are associated with low body weight and low body fat mass. The relationship between exercise and body-weight control is complex and incompletely understood. Regular exercise may decrease energy balance through an increase in energy expenditure or an increase in fat oxidation. It may also contribute to weight loss by modulating nutrient intake. An intriguing question that remains unresolved is whether changes in nutrient intake or body composition secondarily affect spontaneous physical activity. If this were the case, physical activity would represent a major adaptative mechanism for body-weight control.