Glucose Tolerance Tests

Glucose tolerance tests (GTT) can provide an index of pancreatic islet sensitivity to changes in plasma glucose. If insulin does not regulate blood glucose levels in these animals, one would expect an impaired response in which animals do not closely regulate their blood glucose levels. To test this, glucose was administered intravenously (IV) as a 50% solution over a 2- to 4-minute period in a standard dose of 25 g or 0.5 g glucose/kg body weight, and the disappearance rate (K) of glucose was measured over time. Feeding mammals normally have K values of 2.3 or greater in contrast to fasting animals, which have K values of 1.0 or less. The glucose tolerance profile for five seals at weaning and after 8 weeks of fasting is shown in figure 21.2. K values were £ 1.0 for all seals. This profile is similar to that seen in obese and diabetic humans (Salans, Knittle, and Hirsch 1983). Normal (nonobese) mammals would restore euglycemia within 60 to 90 minutes of the glucose injection due to an acute insulin response.

Impaired glucose clearance (K £ 1.0) and the total lack of an insulin response to a glucose injection were virtually identical for pups at weaning and after fasting 8 to 11 weeks. These data indicated that these seals were adapted for fasting, that is, they switched to fat oxidation metabolism, prior to weaning.

In other mammalian neonates, the transition from the glucose-based metabolism of the fetus to the high fat milk diet of the neonate is accompanied by an increase in gluconeogenesis and fatty acid oxidation and a decrease in hepatic lipogenesis in the perinatal period (Kalhan 1992). As carbohydrate is introduced into the diet, the neonate decreases its reliance on de novo synthesis of glucose and increases insulin secretion. Elephant seal milk does not contain carbohydrate; in fact, the fat content is at its highest just prior to weaning. Thus, the suckling elephant seal neonate cannot develop the ability to secrete or utilize insulin for carbohydrate uptake into tissues.

Impaired insulin secretion and tissue insensitivity to insulin are correlated with high body fat levels (and high fat diets) in other mammals. We

Fig. 21.2
Glucose tolerance test for five elephant seal pups just prior to weaning (closed
symbols) and after 8 weeks of fasting (open symbols). The mean glucose
response is represented by the square symbols (solid line). The mean insulin
response is represented by the triangle and hourglass symbols. At time zero,
a bolus injection of 25 g glucose in a 50% saline solution was injected
intravenously. For purposes of clarity, the largest standard deviations for
glucose and insulin are shown as vertical bars.

investigated the effect of body fat on the insulin response to a glucose challenge by comparing glucose clearance rates (K) in pups with known body weights, body composition, and age (Kirby and Ortiz 1989). It proved to be very difficult to separate changes in body fat levels from changes in age. Virtually all seals larger than 100 kg body weight at weaning had a fat mass of 48 to 50%. Seals smaller than 90 kg at weaning had lower body fat levels (< 40%). However, all seals, regardless of weaning mass, age, and duration of fasting, had impaired glucose clearance values less than 1.0 with little or no insulin response to the glucose injection. Glucose clearance values estimated from figures in harbor seal and Weddell seal studies were also less than 1.0 (Hochachka et al. 1979; Robin et al. 1981).