Case Report: Increased Insulin Sensitivity in Tumor Hypoglycemia in a Diabetic Patient: Glucose Metabolism in Tumor Hypoglycemia

Can "big" insulin-like growth factor II in serum of tumor patients account for the development of extrapancreatic tumor hypoglycemia?

“…However, big IGF II in the serum and the tumor of this patient was not reported. Within the same context, Barzilai et al (42) described a diabetic patient with a hepatoma subsequent to hemochromatosis and cirrhosis who lost dependence on insulin and experienced episodes of hypoglycemia. The insulin dose-response curve in this patient as determined by euglycemic clamp technique was shifted to the left, and steady state glucose consumption was 50% higher than in normal control subjects.…”

“…2 ml of normal or tumor serum was passed over a Sephadex G-200 (Pharmacia LKB Biotechnology Inc., Uppsala, Sweden) column (2.2 x 70 cm, flow rate 10 ml/h) in Dulbecco's buffer, pH 7.4, containing 20 mg/ 100 ml of NaN3. Fractions 51-64, 65-71, and 72-84 corresponding to the elution ranges of the 150-and 50-kD IGFBP complexes (as determined from the radiochromatographic pattern of normal and tumor serum preequilibrated with 125I-rhIGF II and gel filtered over the same Sephadex G-200 column) and fractions eluting before (35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50) and after (85-95 and 96-115) the two complexes (2 mg of HSA was added to fractions 80-115 to prevent adsorption of IGF to the tubes) were pooled, dialysed against 0.1 M NH4HCO3 in Spectrapor dialysis tubing (molecular weight cut-off, 3,500), lyophilized, and dissolved in 2 ml Krebs-Ringer-Hepes buffer, pH 7.4. The biological activity in each pool was determined in the presence of0.3 Ml of insulin antiserum (neutralizing capacity 0.4 mU) in the rat fat-cell assay (13).…”

Role of Insulin-Like Growth Factor II and IGF Binding Proteins in Extrapancreatic Tumor Hypoglycemia

“…This leads to stimulation of glucose con sumption in skeletal muscle via the insulin or the type I IGF receptor, and to suppression of hepatic glucose pro duction and lipolysis in adipose tissue via the insulin receptor, and, finally, to sustained hypoglycemia. In creased glucose utilization may further be enhanced by 3 other mechanisms: (1) Increased glucose consumption by the tumor itself (possibly by an auto-/paracrine action of big IGF II secreted by the tumor); (2) low serum FFA lev els which favor glucose uptake in skeletal muscle via the Randle cycle [37], and (3) increased insulin sensitivity resulting from upregulation of insulin receptors in the presence of the low serum insulin levels [38,39], Thus, oversecretion of big IGF II by the tumor creates a vicious cycle.…”

Tumours producing hypoglycaemia

“…This is, however, unlikely to be the explanation for the increased insulin sensitivity that was held to account for the occurrence of (insulin-induced) hypoglycaemia in an insulin-dependent diabetic patient after he developed a primary hepatoma (Barzilai et al 1991) since in this patient the sole source of insulin had been from a bottle. Similarly, in a case described by Sturrock et al (1997), in which the IGF-II:IGF-I ratio was high as a result of a pancreatic carcinoma, spontaneous hypoglycaemia developed late in the course of her illness necessitating discontinuation of insulin therapy.…”