Reversal of enhanced pancreatic cancer growth in diabetes by insulin.
BACKGROUND
Epidemiologic and animal studies have linked pancreatic cancer growth with both diabetes and fat intake. This study examined the influence of insulin treatment on pancreatic cancer growth in diabetes. Diabetes-induced elevations in levels of glucose and free fatty acids were correlated with enhanced tumor growth both in vivo and in vitro.


METHODS
Hamsters were divided into three groups: control (n = 15), streptozocin-diabetic (n = 20), or insulin-treated diabetic (n = 20). Diabetes was induced with streptozocin and treated with a continuous subcutaneous infusion of insulin delivered via osmotic pumps. Five x 10(5) H2T hamster pancreatic cancer cells were implanted into the cheek pouch. Levels of plasma glucose and fatty acids were measured, and their effect on H2T cell division was assessed in vitro with a spectrophotometric cell proliferation assay.


RESULTS
Levels of plasma glucose and fatty acids were elevated in streptozocin-diabetic animals and normalized with insulin treatment. After 21 days of growth, tumor weight was 36 mg in the control group, 156 mg in the diabetic group (p < 0.01 versus other groups), and 33 mg in the insulin-treated diabetic group. In vitro dose-dependent promotion of cell growth was shown for glucose (250%), linoleic acid (287%), linolenic acid (169%), and oleic acid (98%).


CONCLUSIONS
Insulin ameliorated enhanced tumor growth in this model of diabetes. Glucose and free fatty acids mobilized during diabetes may serve as fuel for established pancreatic cancers.
Fisher
W E
WE
Department of Surgery, Ohio State University, Columbus 43210, USA.
Boros
L G
LG
Schirmer
W J
WJ
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D006224:Cricetinae; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications*; D005227:Fatty Acids / Q000097:blood; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D008647:Mesocricetus; D010190:Pancreatic Neoplasms / Q000150:complications* / Q000473:pathology*; D014407:Tumor Cells, Cultured
D001786:Blood Glucose; D005227:Fatty Acids; D007328:Insulin