Evidence that amylin stimulates lipolysis in vivo: a possible mediator of induced insulin resistance.

The present study investigated the role of amylin in lipid metabolism and its possible implications for insulin resistance. In 5- to 7-h-fasted conscious rats, infusion of rat amylin (5 nmol/h for 4 h) elevated plasma glucose, lactate, and insulin (P <0.05 vs. control, repeated-measures ANOVA) with peak values occurring within 60 min. Despite the insulin rise, plasma nonesterified fatty acids (NEFA) and glycerol were also elevated (P < 0.001 vs. control), and these elevations (80% above basal) were sustained over the 4-h infusion period. Although unaltered in plasma, triglyceride content in liver was increased by 28% (P < 0.001) with a similar tendency in muscle (18%, P = 0.1). Infusion of the rat amylin antagonist amylin-(8-37) (125 nmol/h) induced opposite basal plasma changes to amylin, i.e., lowered plasma NEFA, glycerol, glucose, and insulin levels (all P < 0.05 vs. control); additionally, amylin-(8-37) blocked amylin-induced elevations of these parameters (P < 0.01). Treatment with acipimox (10 mg/kg), an anti-lipolytic agent, before or after amylin infusion blocked amylin's effects on plasma NEFA, glycerol, and insulin but not on glucose and lactate. We conclude that amylin could exert a lipolytic-like action in vivo that is blocked by and is opposite to effects of its antagonist amylin-(8-37). Further studies are warranted to examine the physiological implications of lipid mobilization for amylin-induced insulin resistance.

Abnormal muscle fructose bisphosphatase activity in malnourished cancer patients.

Malnourished patients without cancer have abnormal glucose metabolism, low activities of the key enzymes of glycolysis in muscle, and abnormal muscle fiber-type distribution. Malnutrition in cancer is also associated with altered glucose metabolism, and therefore muscle enzyme activities and fiber types were measured in 17 malnourished patients with gastrointestinal cancer (weight loss, 18.1% +/- 7.9 SD). These patients were matched with 17 depleted noncancer patients (weight loss, 22.8% +/- 10.25 SD) and 17 normal controls. Results of in vitro measurement of the maximal activity of phosphofructokinase (PFK), hexokinase (HK), and oxogluterate dehydrogenase (OGD) were similar in both undernourished groups and lower than that of normal controls. Both groups also had reduced Type II fiber size and number. The activity of fructose bisphosphatase (FBP) was significantly higher in cancer patients (0.62 mu ml min-1 g +/- 0.26 SD) than in noncancer patients (0.39 +/- 0.15), but similar to that in controls (0.65 +/- 0.29). As FBP is involved in substrate cycling, inappropriately high activity reflects an inability to adapt to malnutrition that could lead to high rates of cycling and wasteful energy expenditure at times of maximal activation of the cycle.