Abstract
The diabetes that frequently occurs in pancreatic cancer patients is characterized by profound peripheral insulin resistance. The intracellular mechanism of this insulin resistance was investigated in skeletal muscle biopsies from pancreatic cancer patients with or without diabetes and control subjects. Insulin receptor (IR) binding, tyrosine kinase activity, IR messenger RNA (mRNA), IR substrate-1 content, GLUT-4, and GLUT-4 mRNA content were all normal in pancreatic cancer patients. In contrast, multiple defects in glycogen synthesis were found in pancreatic cancer patients, especially in those with diabetes. Glycogen synthase I activity, total activity, and mRNA levels were significantly decreased in pancreatic cancer patients compared with controls. The fractional velocity of glycogen synthase was decreased only in the diabetic pancreatic cancer group. Glycogen phosphorylase a and b activities were increased in diabetic pancreatic cancer patients, but glycogen phosphorylase mRNA levels were not significantly different. The insulin resistance associated with pancreatic cancer is associated with a post-IR defect, which impairs skeletal muscle glycogen synthesis and glycogen storage.
Publication types
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Clinical Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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Blotting, Western
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Diabetes Mellitus / metabolism
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Female
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Fungal Proteins / genetics
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Fungal Proteins / metabolism
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GTPase-Activating Proteins
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Glucose Transporter Type 4
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Glycogen Synthase / genetics
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Glycogen Synthase / metabolism
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Humans
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Insulin Resistance / genetics
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Insulin Resistance / physiology*
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Male
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Middle Aged
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Monosaccharide Transport Proteins / genetics
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Monosaccharide Transport Proteins / metabolism
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Muscle Proteins*
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Muscle, Skeletal / metabolism
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Pancreatic Neoplasms / genetics
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Pancreatic Neoplasms / pathology
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Pancreatic Neoplasms / physiopathology*
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Phosphorylases / genetics
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Phosphorylases / metabolism
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / metabolism
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RNA, Messenger / metabolism
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Receptor, Insulin / genetics
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Receptor, Insulin / metabolism
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Repressor Proteins*
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Reverse Transcriptase Polymerase Chain Reaction
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Saccharomyces cerevisiae Proteins*
Substances
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Fungal Proteins
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GTPase-Activating Proteins
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Glucose Transporter Type 4
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IRA1 protein, S cerevisiae
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Monosaccharide Transport Proteins
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Muscle Proteins
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RNA, Messenger
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Repressor Proteins
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SLC2A4 protein, human
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Saccharomyces cerevisiae Proteins
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Phosphorylases
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Glycogen Synthase
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Protein-Tyrosine Kinases
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Receptor, Insulin