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PMID:12663463

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Citation

Gao, Y, Walder, K, Sunderland, T, Kantham, L, Feng, HC, Quick, M, Bishara, N, de Silva, A, Augert, G, Tenne-Brown, J and Collier, GR (2003) Elevation in Tanis expression alters glucose metabolism and insulin sensitivity in H4IIE cells. Diabetes 52:929-34

Abstract

Increased hepatic glucose output and decreased glucose utilization are implicated in the development of type 2 diabetes. We previously reported that the expression of a novel gene, Tanis, was upregulated in the liver during fasting in the obese/diabetic animal model Psammomys obesus. Here, we have further studied the protein and its function. Cell fractionation indicated that Tanis was localized in the plasma membrane and microsomes but not in the nucleus, mitochondria, or soluble protein fraction. Consistent with previous gene expression data, hepatic Tanis protein levels increased more significantly in diabetic P. obesus than in nondiabetic controls after fasting. We used a recombinant adenovirus to increase Tanis expression in hepatoma H4IIE cells and investigated its role in metabolism. Tanis overexpression reduced glucose uptake, basal and insulin-stimulated glycogen synthesis, and glycogen content and attenuated the suppression of PEPCK gene expression by insulin, but it did not affect insulin-stimulated insulin receptor phosphorylation or triglyceride synthesis. These results suggest that Tanis may be involved in the regulation of glucose metabolism, and increased expression of Tanis could contribute to insulin resistance in the liver.

Links

PubMed

Keywords

Amino Acid Sequence; Animals; Cell Fractionation; Cell Membrane/chemistry; Cell Nucleus/chemistry; Diabetes Mellitus/metabolism; Gene Expression; Gerbillinae; Glucose/metabolism; Glycogen/analysis; Glycogen/biosynthesis; Insulin/pharmacology; Liver/metabolism; Liver/ultrastructure; Membrane Proteins/chemistry; Membrane Proteins/genetics; Membrane Proteins/physiology; Microsomes, Liver/chemistry; Mitochondria, Liver/chemistry; Molecular Sequence Data; Obesity/metabolism; Peptide Fragments/chemistry; Phosphoenolpyruvate Carboxykinase (GTP)/genetics; Phosphorylation; Receptor, Insulin/metabolism; Transfection; Triglycerides/biosynthesis; Tumor Cells, Cultured

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:SELS

located_in

GO:0005886: plasma membrane

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SELS

involved_in

GO:0032869: cellular response to insulin stimulus

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SELS

involved_in

GO:0045719: negative regulation of glycogen biosynthetic process

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SELS

involved_in

GO:0046325: negative regulation of glucose import

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SELS

involved_in

GO:0006111: regulation of gluconeogenesis

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SELS

part_of

GO:0005886: plasma membrane

ECO:0000304: author statement supported by traceable reference used in manual assertion

C

Seeded From UniProt

complete


See also

References

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