Biomedical subjects

J S Thresher

Publications and source records attributed to J S Thresher.

6 recordsLinked to original sources

PubMed2001

A high-sucrose diet increases gluconeogenic capacity in isolated periportal and perivenous rat hepatocytes.

A high-sucrose (SU) diet increases gluconeogenesis (GNG) in the liver. The present study was conducted to determine the contribution of periportal (PP) and perivenous (PV) cell populations to this SU-induced increase in GNG. Male Sprague-Dawley rats were fed an SU (68% sucrose) or starch (ST, 68% starch) diet for 1 wk, and hepatocytes were isolated from the PP or PV region of the liver acinus. Hepatocytes were incubated for 1 h in the presence of various gluconeogenic substrates, and glucose release into the medium was used to estimate GNG. When incubated in the presence of 5 mM lactate, which enters GNG at the level of pyruvate, glucose release (nmol x h(-1) x mg(-1)) was significantly increased by the SU diet in both PP (84.8 +/- 3.4 vs. 70.4 +/- 2.6) and PV (64.3 +/- 2.5 vs. 38.2 +/- 2.1) cells. Addition of palmitate (0.5 mM) increased glucose release from lactate in PP cells by 11.6 +/- 0.5 and 20.6 +/- 1.5% and in PV cells by 11.0 +/- 4.4 and 51.1 +/- 9.1% in SU and ST, respectively. When cells were incubated with 5 mM dihydroxyacetone (DHA), which enters GNG at the triosephosphate level, glucose release was significantly increased by the SU diet in both cell types. In contrast, glucose release from fructose (0.5 mM) was significantly increased by the SU diet in PV cells only. These changes in glucose release were accompanied by significant increases in the maximal specific activities of glucose-6-phosphatase (G-6-Pase) and phosphoenolpyruvate carboxykinase (PEPCK) in both PP and PV cells. These data suggest that the SU diet influences GNG in both PP and PV cell populations. It appears that SU feeding produces changes in GNG via alterations in at least two critical enzymes, G-6-Pase and PEPCK.

Animals↗

PubMed2001

Increased pyruvate flux capacities account for diet-induced increases in gluconeogenesis in vitro.

High-fat (HF) and high-sucrose (SU) diets increase gluconeogenesis. The present study was designed to determine the contributions of pyruvate dehydrogenase, pyruvate carboxylase, phosphoenolpyruvate carboxykinase (PEPCK), and pyruvate kinase fluxes to this accelerated gluconeogenesis (GNEO) in the absence and presence of fatty acids. Male Sprague-Dawley rats were fed an HF, SU, or starch (ST) diet for 1 wk, and hepatocytes or mitochondria were isolated. In the absence of palmitate, the tracer estimated rates of GNEO (nmol. min(-1). mg(-1)) were elevated in hepatocytes isolated from SU (32.3 +/- 1.8) and HF (35.4 +/- 1.8) vs. ST (22.8 +/- 1.5). Pyruvate carboxylase and PEPCK flux rates (nmol. min(-1). mg(-1)) were increased in the SU (47.5 +/- 2.2 and 34.8 +/- 1.5) and HF (49.4 +/- 1.8 and 38.2 +/- 1.8) groups compared with the ST group (32.8 +/- 3.2 and 44.3 +/- 2.0). Palmitate (250-1,000 microM) stimulation of these fluxes was not significantly different among groups. Bromopalmitate, an inhibitor of fat oxidation, abolished differences in GNEO, pyruvate carboxylase, and PEPCK fluxes in HF and SU vs. ST. In isolated mitochondria, pyruvate carboxylation and palmitoyl carnitine oxidation were not significantly different among groups. The results of this study suggest that the increased gluconeogenic flux observed with HF and SU diets is associated with an increased pyruvate flux through pyruvate carboxylase and PEPCK. Moreover, the ability of bromopalmitate to normalize gluconeogenic fluxes suggests that endogenous fatty acids contribute to diet-induced increases in GNEO.

Animals↗

PubMed2001

Hyperglycemia compensates for diet-induced insulin resistance in liver and skeletal muscle of rats.

High-fat and high-sucrose diets increase the contribution of gluconeogenesis to glucose appearance (glc R(a)) under basal conditions. They also reduce insulin suppression of glc R(a) and insulin-stimulated muscle glycogen synthesis under euglycemic, hyperinsulinemic conditions. The purpose of the present study was to determine whether these impairments influence liver and muscle glycogen synthesis under hyperglycemic, hyperinsulinemic conditions. Male rats were fed a high-sucrose, high-fat, or low-fat, starch control diet for either 1 (n = 5-7/group) or 5 wk (n = 5-6/group). Studies involved two 90-min periods. During the first, a basal period (BP), [6-3H]glucose was infused. In the second, a hyperglycemic period (HP), [6-3H]glucose, [6-14C]glucose, and unlabeled glucose were infused. Plasma glucose (BP: 111.2 +/- 1.5 mg/dl; HP: 172.3 +/- 1.5 mg/dl), insulin (BP: 2.5 +/- 0.2 ng/ml; HP: 4.9 +/- 0.3 ng/ml), and glucagon (BP: 81.8 +/- 1.6 ng/l; HP: 74.0 +/- 1.3 ng/l) concentrations were not significantly different among diet groups or with respect to time on diet. There were no significant differences among groups in the glucose infusion rate (mg x kg(-1) x min(-1)) necessary to maintain arterial glucose concentrations at approximately 170 mg/dl (pooled average: 6.4 +/- 0.8 at 1 wk; 6.4 +/- 0.7 at 5 wk), percent suppression of glc R(a) (44.4 +/- 7.8% at 1 wk; 63.2 +/- 4.3% at 5 wk), tracer-estimated net liver glycogen synthesis (7.8 +/- 1.3 microg x g liver(-1) x min(-1) at 1 wk; 10.5 +/- 2.2 microg x g liver(-1) x min(-1) at 5 wk), indirect pathway glycogen synthesis (3.7 +/- 0.9 microg x g liver(-1) x min(-1) at 1 wk; 3.4 +/- 0.9 microg x g liver(-1) x min(-1) at 5 wk), or tracer-estimated net muscle glycogenesis (1.0 +/- 0.3 microg x g muscle(-1) x min(-1) at 1 wk; 1.6 +/- 0.3 microg x g muscle(-1) x min(-1) at 5 wk). These data suggest that hyperglycemia compensates for diet-induced insulin resistance in both liver and skeletal muscle.

Analysis of Variance↗

PubMed2001

Sucrose diets increase glucose-6-phosphatase and glucose release and decrease glucokinase in hepatocytes.

A high-sucrose diet (SU) decreases insulin action in the liver (Pagliassotti MJ, Shahrokhi KA, and Moscarello M. Am J Physiol Regulatory Integrative Comp Physiol 266: R1637-R1644, 1994). The present study was conducted to characterize the effect of SU on glucagon action in isolated periportal (PP) and perivenous (PV) hepatocytes by measuring glucagon-stimulated glycogenolysis and glucose release. Male rats were fed a SU (68% sucrose) or starch diet (ST, 68% starch) for 1 wk, and hepatocytes were isolated from PP or PV regions (n = 4/diet/cell population). Hepatocytes were incubated for 1 h in the presence of varying concentrations of glucagon (0-100 nM). In PP and PV cells, glucagon stimulation of glucose release and glycogenolysis (sum of glucose release and lactate accumulation) was not significantly different between SU and ST cells. However, in the SU PP cells, glucose release was increased compared with ST PP cells, both in the absence of glucagon (76.1 +/- 4 vs. 54.8 +/- 3 nmol x h(-1) x mg cell wet x wt(-1)) and at all glucagon concentrations. In SU-fed PV cells, glucose release was increased compared with ST PV cells in the absence of glucagon (79.3 +/- 5 vs. 56.4 +/- 5 nmol x h(-1) x mg cell wet x wt(-1)) and at low glucagon concentrations. Maximal glucose-6-phosphatase activity (in nmol x min(-1) x mg protein(-1)) was elevated in SU compared with ST cells (61.4 +/- 3 vs. 37.5 +/- 4 in PP and 37.5 +/- 4 vs. 29.5 +/- 3 in PV cells). In contrast, maximal glucokinase activity (in nmol x min(-1) x mg protein(-1)) was elevated in ST compared with SU cells (15.9 +/- 2 vs. 12.1 +/- 1 in PP and 19.4 +/- 2 vs. 14.2 +/- 1 in PV cells). These data demonstrate that SU increases the capacity for glucose release in both PP and PV hepatocytes, in part because of reciprocal changes in glucose-6-phosphatase and glucokinase.

Animals↗

PubMed2000

Comparison of the effects of sucrose and fructose on insulin action and glucose tolerance.

The purpose of the present study was to determine whether fructose is the nutrient mediator of sucrose-induced insulin resistance and glucose intolerance. Toward this end, male rats were fed a purified starch diet (68% of total calories) for a 2-wk baseline period. After this, rats either remained on the starch (ST) diet or were switched to a sucrose (SU, 68% of total calories), fructose/glucose (F/G, 34/34% of total calories), or fructose/starch (F/ST, 34/34% of total calories) diet for 5 wk. Rats then underwent either an intravenous glucose tolerance test (n = 10/diet) or a euglycemic, hyperinsulinemic clamp (n = 8 or 9/diet). Incremental glucose and insulin areas under the curve in SU, F/G, and F/ST were on average 61 and 29% greater than ST, respectively, but not significantly different from one another. During clamps, glucose infusion rates (mg. kg(-1). min(-1)) required to maintain euglycemia were significantly lower (P < 0.05) in SU, F/G, and F/ST (13.4 +/- 0.9, 9. 5 +/- 1.7, 11.3 +/- 1.3, respectively) compared with ST (22.8 +/- 1. 1). Insulin suppression of glucose appearance (mg. kg(-1). min(-1)) was significantly lower (P < 0.05) in SU, F/G, and F/ST (5.6 +/- 0.5, 2.2 +/- 1.2, and 6.6 +/- 0.7, respectively) compared with ST (9.6 +/- 0.4). Insulin-stimulated glucose disappearance (mg. kg(-1). min(-1)) was significantly lower (P < 0.05) in SU, F/G, and F/ST (17. 9 +/- 0.6, 16.2 +/- 1.3, 15.3 +/- 1.8, respectively) compared with ST (24.7 +/- 1.2). These data suggest that fructose is the primary nutrient mediator of sucrose-induced insulin resistance and glucose intolerance.

Adipose Tissue↗

PubMed1998

Menhaden oil prevents but does not reverse sucrose-induced insulin resistance in rats.

Although fish oil supplementation may prevent the onset of diet-induced insulin resistance in rats, it appears to worsen glycemic control in humans with existing insulin resistance. In the present study, the euglycemic, hyperinsulinemic (4x basal) clamp technique with [3-3H]glucose and 2-deoxy-[1-14C]glucose was used to directly compare the ability of fish oil to prevent and reverse sucrose-induced insulin resistance. In study 1 (prevention study), male Wistar rats were fed a purified high-starch diet (68% of total energy), high-sucrose diet (68% of total energy), or high-sucrose diet in which 6% of the fat content was replaced by menhaden oil for 5 wk. In study 2 (reversal study), animals were fed the high-starch or high-sucrose diets for 5 wk and then the sucrose animals were assigned to one of the following groups for an additional 5 wk: high starch, high sucrose, or high sucrose with 6% menhaden oil. Rats fed the high-starch diet for 10 wk served as controls. In study 3 (2nd reversal study), animals followed a similar diet protocol as in study 2; however, the reversal period was extended to 15 wk. In study 1, the presence of the fish oil in the high-sucrose diet prevented the development of insulin resistance. Glucose infusion rates (GIR, mg.kg-1.min-1) were 17.0 +/- 0.9 in starch, 10.6 +/- 1.7 in sucrose, and 15.1 +/- 1.5 in sucrose with fish oil animals. However, in study 2, this same diet was unable to reverse sucrose-induced insulin resistance (GIR, 16.7 +/- 1.4 in starch, 7.1 +/- 1.5 in sucrose, and 4.8 +/- 0.9 in sucrose with fish oil animals). Sucrose-induced insulin resistance was reversed in rats that were switched back to the starch diet (GIR, 18.6 +/- 3.0). Results from study 3 were similar to those observed in study 2. In summary, fish oil was effective in preventing diet-induced insulin resistance but not able to reverse it. A preexisting insulin-resistant environment interferes with the positive effects of menhaden oil on insulin action.

Animals↗