Chronic effect of fatty acids on insulin release is not through the alteration of glucose metabolism in a pancreatic beta-cell line (βHC9)

Liang, Yin; Buettger, Carol; Berner, Donna K; Matschinsky, Franz M.

doi:10.1007/s001250050783

Cited by 71 publications

(51 citation statements)

References 32 publications

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“…In addition, the fold stimulation due to 16.7 mmol/l glucose was reduced from 14 times basal in control cells to four-to fivefold in cells pretreated with either lipid. The increased basal secretion and diminished fold increase to high glucose are comparable to numerous studies using lipid-pretreated islets or ␤-cell lines (7,11,12,(17)(18)(19)(20). However, our results additionally suggested that oleate and palmitate were not entirely equivalent in their effects.…”

Section: Resultssupporting

confidence: 72%

Expression Profiling of Palmitate- and Oleate-Regulated Genes Provides Novel Insights Into the Effects of Chronic Lipid Exposure on Pancreatic β-Cell Function

Busch

Cordery²,

Denyer³

et al. 2002

Diabetes

175

139

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Chronic lipid exposure is implicated in ␤-cell dysfunction in type 2 diabetes. We therefore used oligonucleotide arrays to define global alterations in gene expression in MIN6 cells after 48-h pretreatment with oleate or palmitate. Altogether, 126 genes were altered >1.9-fold by palmitate, 62 by oleate, and 46 by both lipids. Importantly, nine of the palmitate-regulated genes are known to be correspondingly changed in models of type 2 diabetes. A tendency toward ␤-cell de-differentiation was also apparent with palmitate: pyruvate carboxylase and mitochondrial glycerol 3-phosphate dehydrogenase were downregulated, whereas lactate dehydrogenase and fructose 1,6-bisphosphatases were induced. Increases in the latter (also seen with oleate), along with glucosamine-phosphate N-acetyl transferase, imply upregulation of the hexosamine biosynthesis pathway in palmitate-treated cells. However, palmitate also increased expression of calcyclin and 25-kDa synaptosomal-associated protein (SNAP25), which control distal secretory processes. Consistent with these findings, secretory responses to noncarbohydrate stimuli, especially palmitate itself, were upregulated in palmitate-treated cells (much less so with oleate). Indeed, glucose-stimulated secretion was slightly sensitized by chronic palmitate exposure but inhibited by oleate treatment, whereas both lipids enhanced basal secretion. Oleate and palmitate also induced expression of chemokines (MCP-1 and GRO1 oncogene) and genes of the acute phase response (

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Section: Resultssupporting

confidence: 72%

Expression Profiling of Palmitate- and Oleate-Regulated Genes Provides Novel Insights Into the Effects of Chronic Lipid Exposure on Pancreatic β-Cell Function

Busch

Cordery²,

Denyer³

et al. 2002

Diabetes

175

139

View full text Add to dashboard Cite

show abstract

“…The FFA concentrations most commonly used to produce the lipotoxicity model were between 0.25 to 2.0 mM for a duration of 48 to 96 h [33][34][35][36][37]. Our results in rat islets as well as in the INS-1E cell line are consistent with the literature.…”

Section: Discussionsupporting

confidence: 89%

Stevioside Counteracts Beta-Cell Lipotoxicity without Affecting Acetyl CoA Carboxylase

Chen¹,

Jeppesen²,

Nordentoft³

et al. 2006

Rev Diabetic Stud

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■ AbstractChronic exposure to high levels of free fatty acids impairs beta-cell function (lipotoxicity). Then basal insulin secretion (BIS) is increased and glucose-stimulated insulin secretion (GSIS) is inhibited. Acetyl CoA carboxylase (ACC) acts as the sensor for insulin secretion in pancreatic beta-cells in response to glucose and other nutrients. Stevioside (SVS), a diterpene glycoside, has recently been shown to prevent glucotoxic effect by regulating ACC activity. The aim of this study was to investigate whether SVS can alleviate impaired beta-cell function by regulating ACC activity. We exposed isolated rat islets and the clonal beta-cell line, INS-1E, to palmitate concentrations of 1.0 or 0.6 mM, respectively, for a period of 24 h to 120 h. The results showed that lipotoxicity occurred in rat islets after 72 h exposure to 1.0 mM palmitate. The lipotoxicity was counteracted by 10 -6 M SVS (n = 8, p < 0.001). Similar results were obtained in INS-1E cells. Neither SVS nor palmitate had any effect on the gene expression of ACC, insulin 2, and glucose transporter 2 in INS-1E cells. In contrast, palmitate significantly increased the gene expression of carnitine palmitoyl transporter 1 (n = 6, p = 0.003). However, the addition of SVS to palmitate did not counteract this effect (n = 6, p = 1.0). During lipotoxicity, SVS did not alter levels of ACC protein, phosphorylated-ACC, ACC activity or glucose uptake. Our results showed that SVS counteracts the impaired insulin secretion during lipotoxicity in rat islets as well as in INS-1E cells without affecting ACC activity.

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“…A magnetic stirrer within the respirometer kept the cells in suspension. (14). Briefly, 10 6 cells were washed once in PBS prior to resuspension in 1 ml of Krebs buffer and incubation for 30 min at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Growth Factors Can Influence Cell Growth and Survival through Effects on Glucose Metabolism

Heiden

Plas

Rathmell

et al. 2001

Molecular and Cellular Biology

480

411

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Cells from multicellular organisms are dependent upon exogenous signals for survival, growth, and proliferation. The relationship among these three processes was examined using an interleukin-3 (IL-3)-dependent cell line. No fixed dose of IL-3 determined the threshold below which cells underwent apoptosis. Instead, increasing growth factor concentrations resulted in progressive shortening of the G 1 phase of the cell cycle and more rapid proliferative expansion. Increased growth factor concentrations also resulted in proportional increases in glycolytic rates. Paradoxically, cells growing in high concentrations of growth factor had an increased susceptibility to cell death upon growth factor withdrawal. This susceptibility correlated with the magnitude of the change in the glycolytic rate following growth factor withdrawal. To investigate whether changes in the availability of glycolytic products influence mitochondrion-initiated apoptosis, we artificially limited glycolysis by manipulating the glucose levels in the medium. Like growth factor withdrawal, glucose limitation resulted in Bax translocation, a decrease in mitochondrial membrane potential, and cytochrome c redistribution to the cytosol. In contrast, increasing cell autonomous glucose uptake by overexpression of Glut1 significantly delayed apoptosis following growth factor withdrawal. These data suggest that a primary function of growth factors is to regulate glucose uptake and metabolism and thus maintain mitochondrial homeostasis and enable anabolic pathways required for cell growth. Consistent with this hypothesis, expression of the three genes involved in glucose uptake and glycolytic commitment, those for Glut1, hexokinase 2, and phosphofructokinase 1, was found to rapidly decline to nearly undetectable levels following growth factor withdrawal.

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Chronic effect of fatty acids on insulin release is not through the alteration of glucose metabolism in a pancreatic beta-cell line (βHC9)

Cited by 71 publications

References 32 publications

Expression Profiling of Palmitate- and Oleate-Regulated Genes Provides Novel Insights Into the Effects of Chronic Lipid Exposure on Pancreatic β-Cell Function

Expression Profiling of Palmitate- and Oleate-Regulated Genes Provides Novel Insights Into the Effects of Chronic Lipid Exposure on Pancreatic β-Cell Function

Stevioside Counteracts Beta-Cell Lipotoxicity without Affecting Acetyl CoA Carboxylase

Growth Factors Can Influence Cell Growth and Survival through Effects on Glucose Metabolism

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