Elevation in Tanis expression alters glucose metabolism and insulin sensitivity in H4IIE cells.
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.
Gao
Yuan
Y
Metabolic Research Unit, School of Health Sciences, Deakin University, Victoria, Australia. gao@deakin.edu.au
Walder
Ken
K
Sunderland
Terry
T
Kantham
Lakshmi
L
Feng
Helen C
HC
Quick
Melissa
M
Bishara
Natalie
N
de Silva
Andrea
A
Augert
Guy
G
Tenne-Brown
Janette
J
Collier
Gregory R
GR
D000595:Amino Acid Sequence; D000818:Animals; D002458:Cell Fractionation; D002462:Cell Membrane / Q000737:chemistry; D002467:Cell Nucleus / Q000737:chemistry; D003920:Diabetes Mellitus / Q000378:metabolism; D015870:Gene Expression; D005849:Gerbillinae; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000032:analysis / Q000096:biosynthesis; D007328:Insulin / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D008862:Microsomes, Liver / Q000737:chemistry; D008930:Mitochondria, Liver / Q000737:chemistry; D008969:Molecular Sequence Data; D009765:Obesity / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics; D010766:Phosphorylation; D011972:Receptor, Insulin / Q000378:metabolism; D014162:Transfection; D014280:Triglycerides / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D007328:Insulin; D008565:Membrane Proteins; D010446:Peptide Fragments; D014280:Triglycerides; C457119:tanis protein, Psammomys obesus; D006003:Glycogen; D011972:Receptor, Insulin; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D005947:Glucose