Search PubMed⌕ Search

Biomedical subjects

Z Q Shi

Publications and source records attributed to Z Q Shi.

54 records · Page 3Linked to original sources
PubMed1994

Insulin-like growth factor-I and insulin have no differential effects on glucose production and utilization under conditions of hyperglycemia.

We have previously shown that in moderately hyperglycemic depancreatized dogs, a glucose-lowering infusion of insulin-like growth factor-I (IGF-I) increased glucose utilization and lactate more, and suppressed glucose production and lipolysis less, than an equipotent glucose-lowering dose of insulin. Similar differences have been observed by others in nondiabetic and diabetic rats. To determine whether the decline in glycemia was important in detecting differential effects of IGF-I and insulin on glucose turnover, IGF-I (0.43 micrograms/kg.min; n = 6) or insulin (0.9 mU/kg.min; n = 9) were infused for 180 min, while hyperglycemia (approximately 180 mg/dl) was maintained. The decline of plasma glucose specific activity was minimized by using the matched step tracer infusion ([6-3H]- and [2-3H]glucose) method. Our results confirmed the approximately 10% potency of IGF-I on glucose metabolism compared to insulin and the lack of effect of IGF-I on insulin clearance. Under conditions of hyperglycemia, the glucose turnover findings were unexpected; there was no difference in the inhibition of glucose production (difference from basal, 2.7 +/- 0.4 mg/kg.min with IGF-I and 2.4 +/- 0.2 with insulin) or the stimulation of glucose utilization (difference from basal, 4.5 +/- 0.8 mg/kg.min with IGF-I and 4.7 +/- 1.3 with insulin). However, lactate increased more (P < 0.01) with IGF-I (from 1230 +/- 163 to a peak of 1903 +/- 349 microM) than insulin (from 1209 +/- 291 to 1535 +/- 340 microM) despite the same increment in glucose utilization. FFA and glycerol declined more with insulin, but the difference was not significant. IGF-I and insulin suppressed plasma amino acids to an equivalent extent. We concluded that 1) the differential effects of IGF-I and insulin on glucose turnover are masked under conditions of hyperglycemia; and 2) because insulin and IGF-I induced the same increment in glucose utilization, but lactate increased more with IGF-I, IGF-I might affect intracellular glucose metabolism differently from insulin. The failure of IGF-I to induce greater glucose utilization than insulin during hyperglycemia, the greater rise in lactate with IGF-I treatment, and the absence of differential effects on proteolysis indicate that IGF-I might have only limited clinical application in the treatment of diabetes.

Animals↗
PubMed1994

Importance of substrate changes in the decrease of hepatic glucose cycling during insulin infusion and declining glycemia in the depancreatized dog.

We wished to determine whether the elevated glucose cycling (GC) between glucose and glucose-6-phosphate (G<-->G6P) in diabetes can be reversed with acute insulin treatment. In six insulin-deprived, anesthetized, depancreatized dogs, insulin was infused for 6-9 h at a starting dose of 45-150 pmol.kg-1.min-1 to normalize plasma glucose from 23.9 +/- 1.4 to 5.0 +/- 0.4 mmol/l and gradually decreased to and maintained at a basal rate (1.7 +/- 1.0 pmol.kg-1.min-1) during the last 3 h. GC, measured with [2-3H]- and [6-3H]glucose, fell markedly from 15.3 +/- 2.7 and normalized at 1.3 +/- 0.6 mumol.kg-1.min-1 (P < 0.001). This occurred because total hepatic glucose output fell much more (from 41.2 +/- 3.1 to 11.6 +/- 1.2) than did glucose production (from 25.9 +/- 1.9 to 10.3 +/- 1.0 mumol.kg-1.min-1) (both P < 0.01). Freeze-clamped liver biopsies were taken at timed intervals for measurements of hepatic enzymes and substrates. The elevated hepatic hexose-6-phosphate levels decreased with insulin infusion (151 +/- 24 vs. 71 +/- 13 nmol/g, P < 0.01). Maximal activities of glucose-6-phosphatase (G6Pase) (from 17.6 +/- 0.8 to 19.6 +/- 2.6 U/g) and glucokinase (from 1.1 +/- 0.2 to 1.0 +/- 0.2 U/g) did not change. Insulin infusion resulted in a threefold increase (P < 0.05) in the activity of glycogen synthase (active form), but had no effect on hepatic glycogen content.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Prevention of postoperative gastroesophageal reflux by preservation of lower esophageal sphincter in partial esophagectomy.

Postoperative reflux esophagitis is a common complication after partial removal of the esophagus and the whole gastric cardia for reconstruction through esophagogastrostomy. In 10 cases, the lower esophageal sphincter (LES) was preserved for a length of 2.05 +/- 0.33cm (mean +/- S) during partial esophagectomy for benign or malignant lesion at the middle and lower portion of the thoracic esophagus. The mean value of the LES pressures measured two weeks after operations was 2.40 +/- 0.64 kPa (18 +/- 4.8 mmHg) and the postoperative X-ray barium meal examination revealed no evidence of gastroesophageal reflux. Our study suggested that the preserved LES should effectively act as a functional barrier against the development of reflux esophagitis.

Carcinoma, Squamous Cell↗
PubMed1993

Indirect effects of insulin in regulating glucose fluxes.

Metabolism of fuels is driven by the energy demand of the organism and its regulation is influenced by many hormonal and metabolic factors. Insulin is of utmost importance in regulating glucose metabolism by promoting glucose uptake in the insulin-sensitive tissues for energy consumption and/or storage. The effects of insulin on glucose metabolism can be both direct and indirect. Ample evidence has indicated that insulin directly stimulates glucose transport systems in the target tissues. However, the changes in glucose fluxes can also be brought out by indirect effects of insulin which are produced secondary to the insulin-induced changes in other hormones and metabolites. In this chapter, we discussed a number of examples of insulin's indirect effects on glucose metabolism. We demonstrated that insulin can indirectly promote muscle glucose uptake during exercise by restraining the release and oxidation of fatty acids and decrease of hyperglycemia. We have presented some evidence for an indirect regulation of glucose cycling by insulin. We have also demonstrated the importance of the peripheral levels of insulin for insulin-induced inhibition of hepatic glucose production. This presumably indirect effects of peripheral insulin might consist of 1) suppression of the release of energy substrates and gluconeogenic precursors; and 2) suppression of glucagon secretion. In a carbachol-induced stress model, insulin is not required for a putatively neural regulation of an increase in systemic glucose uptake but a "permissive" effect of insulin is essential. These studies underscore the importance of the interactions between insulin and other hormones and metabolites as opposed to insulin's direct actions per se.

Animals↗
PubMed1993

Effects of subbasal insulin infusion on resting and exercise-induced glucose turnover in depancreatized dogs.

beta-Adrenergic blockade suppressed lipolysis and normalized the exercise-induced increments in glucose uptake (GlcU) and metabolic clearance rate (MCR) in alloxan-diabetic dogs with residual insulin, but not in insulin-deprived depancreatized dogs even when combined with methylpalmoxirate (MP), which suppresses fatty acid oxidation. The effects of a minimal amount of insulin (as in the alloxan-diabetic dog), were studied in depancreatized, 24-h insulin-deprived dogs during rest and treadmill exercise (6 km/h, 10% slope) using a 1/4 basal insulin infusion (50 microU.kg-1.min-1, insulin, n = 6) alone, or with MP (20 mg.kg-1.day orally, 2.5 days, MP+insulin, n = 6). At rest, insulin decreased circulating fatty acids (31%) and Glc (13%) and increased GlcU and MCR (86 and 72%). Glc production was unaffected. MP plus insulin markedly suppressed hepatic fatty acid oxidation, decreased Glc (44%) and Glc production (50%), and markedly increased MCR (128%). The exercise-induced increments in MCR were markedly improved only by MP plus insulin but were still lower than in the propranolol-treated alloxan-diabetic dogs. Plasma Glc inversely correlated with the exercise-induced increase in MCR (r = -0.86). We conclude that 1) acute infusion of subbasal insulin improved GlcU in depancreatized dogs at rest but not during exercise; 2) inhibition of fatty acid oxidation combined with subbasal insulin improved the exercise-induced increase in MCR; and 3) the difference in GlcU and MCR between the MP plus insulin-treated depancreatized dogs and the beta-blockade-treated alloxan-diabetic dogs suggests a difference between acute and chronic effects of insulin.

3-Hydroxybutyric Acid↗
PubMed1992

Role of FFA-glucose cycle in glucoregulation during exercise in total absence of insulin.

Muscle contraction in vitro increases glucose uptake (GU), independent of insulin, but in vivo, the exercise-induced increase in GU is impaired in insulin-deficient diabetic dogs. We wished to determine whether, in vivo, suppression of the free fatty acid (FFA)-glucose cycle with methylpalmoxirate (MP, inhibitor of FFA oxidation) alone or combined with propranolol (PRO, beta-blocker) could improve GU during exercise in the absence of insulin. We performed four groups of exercise experiments (6 km/h, 10% slope) in depancreatized insulin-deprived dogs: 1) control (n = 6); 2) MP treated (5 oral doses of 10 mg/kg, twice daily, n = 6); 3) treated with MP+octanoate (OCT; oxidation unaffected by MP, 27 mumol.kg-1.min-1 iv during exercise; n = 5); and 4) MP+PRO treated (5 micrograms.kg-1.min-1 iv during exercise, n = 6). MP abolished ketosis (inhibition of hepatic FFA oxidation), decreased basal glucose production (GP), and increased metabolic clearance of glucose (MCR). During exercise, MP attenuated the increment in GP (P < 0.01), which was reversed by OCT. MP did not affect the exercise-induced increase in GU and MCR. With MP+PRO, FFAs decreased and lactate did not rise during exercise. GP was not further suppressed, but GU and MCR were increased (P < 0.01) to 89 and 31% of normal, respectively. In insulin-deprived depancreatized dogs, glucose cycling was increased to a greater extent than GP, as in type II diabetes. By the end of exercise, glucose cycling increased (P < 0.05), but to a similar extent as GP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Importance of peripheral insulin levels for insulin-induced suppression of glucose production in depancreatized dogs.

It is generally believed that glucose production (GP) cannot be adequately suppressed in insulin-treated diabetes because the portal-peripheral insulin gradient is absent. To determine whether suppression of GP in diabetes depends on portal insulin levels, we performed 3-h glucose and specific activity clamps in moderately hyperglycemic (10 mM) depancreatized dogs, using three protocols: (a) 54 pmol.kg-1 bolus + 5.4 pmol.kg-1.min-1 portal insulin infusion (n = 7; peripheral insulin = 170 +/- 51 pM); (b) an equimolar peripheral infusion (n = 7; peripheral insulin = 294 +/- 28 pM, P < 0.001); and (c) a half-dose peripheral infusion (n = 7), which gave comparable (157 +/- 13 pM) insulinemia to that seen in protocol 1. Glucose production, use (GU) and cycling (GC) were measured using HPLC-purified 6-[3H]- and 2-[3H]glucose. Consistent with the higher peripheral insulinemia, peripheral infusion was more effective than equimolar portal infusion in increasing GU. Unexpectedly, it was also more potent in suppressing GP (73 +/- 7 vs. 55 +/- 7% suppression between 120 and 180 min, P < 0.001). At matched peripheral insulinemia (protocols 2 and 3), not only stimulation of GU, but also suppression of GP was the same (55 +/- 7 vs. 63 +/- 4%). In the diabetic dogs at 10 mM glucose, GC was threefold higher than normal but failed to decrease with insulin infusion by either route. Glycerol, alanine, FFA, and glucagon levels decreased proportionally to peripheral insulinemia. However, the decrease in glucagon was not significantly greater in protocol 2 than in 1 or 3. When we combined all protocols, we found a correlation between the decrements in glycerol and FFAs and the decrease in GP (r = 0.6, P < 0.01). In conclusion, when suprabasal insulin levels in the physiological postprandial range are provided to moderately hyperglycemic depancreatized dogs, suppression of GP appears to be more dependent on peripheral than portal insulin concentrations and may be mainly mediated by limitation of the flow of precursors and energy substrates for gluconeogenesis and by the suppressive effect of insulin on glucagon secretion. These results suggest that a portal-peripheral insulin gradient might not be necessary to effectively suppress postprandial GP in insulin-treated diabetics.

Animals↗
PubMed1992

Effect of diabetes on glucoregulation. From glucose transporters to glucose metabolism in vivo.

Peripheral resistance to insulin is a prominent feature of both insulin-dependent and non-insulin-dependent diabetes. Skeletal muscle is the primary site responsible for decreased insulin-induced glucose utilization in diabetic subjects. Glucose transport is the rate-limiting step for glucose utilization in muscle, and that cellular process is defective in human and animal diabetes. The transport of glucose across the muscle cell plasma membrane is mediated by glucose transporter proteins, and two isoforms (GLUT1 and GLUT4) are expressed in muscle. Insulin acutely increases glucose transport in muscle by selectively stimulating the recruitment of the GLUT4 transporter (but not GLUT1) from an intracellular pool to the plasma membrane. In skeletal muscles of streptozocin-induced diabetic rats, there is a decreased GLUT4 protein content in intracellular and plasma membranes. In these rats, insulin induced the mobilization of GLUT4 from the internal pool, but the incorporation of the transporter protein into the plasma membrane is diminished. Conversely, the content of the GLUT1 transporter increases in the plasma membrane of these diabetic rats. Normalization of glycemia with phlorizin fully restores the amount of GLUT1 and GLUT4 proteins to normal levels in the plasma membrane without altering insulin levels. This suggests that glycemia regulates the number of glucose transporters at the cell surface, GLUT1 varying directly and GLUT4 inversely, to glycemia. The regulatory role of glycemia also can be seen in diabetic dogs in vivo, where correction of hyperglycemia with phlorizin restores, at least in part, the defective metabolic clearance rate of glucose seen in these animals. In addition to acutely stimulating glucose transport in muscle, insulin controls exercise- and possibly stress-mediated glucose uptake in vivo, by preventing hyperglycemia and by restraining the effects of catecholamines on lipolysis and/or muscle glycogenolysis. Finally, we postulated a neural pathway that requires the permissive effect of insulin to increase glucose uptake by the muscle. Thus, insulin, glucose, and neural pathways regulate muscle glucose utilization in vivo and are, therefore, important determinants of glucoregulation in diabetes.

Animals↗
PubMed1989

Development and evaluation of a system of microencapsulation of primary rat hepatocytes.

To determine the in vitro function of microencapsulated hepatocytes, viable hepatocytes were isolated from rats and encapsulated within biocompatible alginate-polylysine membranes for in vitro studies. Urea formation, prothrombin and cholinesterase activity, the incorporation of tritiated leucine into intracellular proteins and the immunolocation of synthesized albumin were monitored in culture. Despite a decrease in some of these activities, the cultured hepatocytes continued to function throughout the 5-week observation period, producing and excreting urea, prothrombin and cholinesterase activity into the medium. In addition, albumin could be demonstrated within encapsulated hepatocytes for up to 5 weeks. Scanning and transmission electron microscopy showed the cells to be embedded within the alginate matrix and to retain a globular shape.

Albumins↗
PubMed1989

Effects of active oxygen generated by DTT/Fe2+ on cardiac Na+/Ca2+ exchange and membrane permeability to Ca2+.

Sarcolemmal vesicles isolated from bovine heart were preincubated at 37 degrees C with an oxygen radical generating system consisting of 1 mM dithiothreitol (DTT) and 50 microM FeSO4. Exposure of the vesicles for 1 to 40 mins stimulated Na+/Ca2+ exchange about 2.5-fold. The DTT/Fe2+ treatment decreased the apparent Km for Ca2+ of Nai+-dependent Ca2+ uptake by 80% (from 63 to 13 microM). The effect on Vmax was much smaller however. The resulting stimulation of exchange activity was diminished by the presence of desferrioxamine (95%) or catalase (60%). In contrast, superoxide dismutase and sodium formate did not prevent the effects of DTT/Fe2+ on the exchanger. Neither Zn2+ nor Ga3+ could replace Fe2+ in the stimulation of Na+/Ca2+ exchange. Passive Ca2+ efflux was determined by first allowing Na+/Ca2+ exchange to continue to plateau values and then diluting the loaded vesicles in the presence of EGTA. Ca2+ leakage from the vesicles was slightly but significantly (P less than 0.05) increased by the action of DTT/Fe2+, the rate constants for the passive Ca2+ efflux being 0.22 and 0.26/min in control and treated groups, respectively. The calcium loading observed in myocytes in ischemia/reperfusion injury suggests that the stimulation of Na+/Ca2+ exchange by active oxygen may moderate the myocardial response to oxygen mediated injuries including ischemia/reperfusion injury. However, the clinical relevance of these phenomena is far from clear as the stimulation depends in part on the Km for Ca2+ prior to treatment.

Adenosine Triphosphatases↗
PubMed1988

Microencapsulated hepatocytes for bioartificial liver support.

Free hepatocytes, harvested from normal rat livers by portal vein collagenase perfusion, were encapsulated within alginate-polylysine membranes and served as a liver support system. The encapsulated hepatocytes remained viable and were able to synthesize protein for up to 3 weeks in culture. Allografts of encapsulated hepatocytes replaced the function of a damaged liver and reduced the mortality rate among rats with galactosamine-induced fulminant hepatic failure.

Albumins↗
PubMed1984

Amino acid disturbances in experimental hepatic coma rats.

In our previous paper (1), we discussed the in-vitro adsorption spectrum of plasma amino acids by coated charcoal hemoperfusion. We now describe the general amino acid disturbances in plasma, CSF and cerebrum in the galactosamine induced hepatic coma model in rats. All aromatic amino acids (AAA) increased significantly in the three compartments studied. Branched chain amino acids (BCAA) were either elevated to a much lesser extent or remained unchanged. The molar ratio of BCAA:AAA was consequently reduced. This is similar to findings in fulminant hepatic failure in human and other animal models. Most of the 20 amino acids analyzed were increased significantly in the plasma. Increases of amino acids were minimal in the brain tissue studied, i.e. the cerebrum.

Amino Acids↗
PubMed1984

Effect of charcoal hemoperfusion on amino acid disturbance in experimental hepatic coma.

Using the galactosamine induced hepatic coma rat model, we studied the effects of coated charcoal hemoperfusion on amino acids in plasma and CSF in grade III hepatic coma. We found that 1 hour of hemoperfusion significantly reduced AAAs and BCAAs in plasma and increased the molar ratio of BCAA:AAA. When rats in grade III coma were treated with 2 consecutive 1-hour hemoperfusions, the substantial reduction of plasma AAAs resulted in a significant decrease of AAA levels in CSF.

Adsorption↗
PubMed1983

In vitro adsorption spectrum of plasma amino acids by coated charcoal hemoperfusion.

In order to clarify whether coated charcoal hemoperfusion is capable of normalizing amino acid disturbances in hepatic coma, in vitro adsorption and in vitro hemoperfusion studies were carried out. We have found that collodion-coated activated charcoal beads preferentially removed much more aromatic acids (AAA) than branched chain amino acids (BCAA). In the in vitro adsorption experiment with 50 microM amino acid standards aqueous solution, 99% of AAAs were removed by charcoal while only 50 to 81% of BCAAs were removed. As the concentration of amino acids in solution was doubled from microM to 100 microM, BCAA removal was halved while about 90% of AAA was still being removed. In vitro hemoperfusion with heparinized blood from hepatic failure rats, the clearance and the removal of AAAs were significantly greater than those of BCAAs. Consequently, the molar ratio of BCAA over AAA was markedly improved from the initial 1.09 to 3.87 after 60 min of hemoperfusion. Thus, we have demonstrated the preferential adsorption of aromatic amino acids by collodion-coated charcoal beads. The correction of BCAA/AAA molar ratio is also demonstrated.

Adsorption↗
PubMedDate not supplied

In vitro culture and transplantation of encapsulated human fetal islets as an artificial endocrine pancreas.

There has been increasing evidence indicating that islet transplantation may offer an ideal endocrine replacement therapy for patients with Type I diabetes mellitus. However, allogenic islets are susceptible to immune rejection. In 1980, Lim and Sun first reported a novel technique of microencapsulation by which pancreatic islets used as transplants could be encapsulated and immunoisolated so as to survive and function for a period of 2-3 weeks. By further improving the biocompatibility of the capsular membrane, Sun's group demonstrated that islet allografts can be protected from rejection for up to 21 months in nonimmunosuppressed, streptozotocin-induced diabetic rats. The biocompatible polymer capsule membrane constitutes a physical barrier to the host's immune system. Permeability of the membrane can be controlled to allow free diffusion of small molecular nutrients, hormones, and metabolites, but exclude lymphocytes, leukocytes, and macromolecular immunoglobulins and complement. Darquy and Reach, in 1985, disclosed the role of the microcapsule membrane in protecting islets from cytotoxic antibodies. Sun's group further demonstrated that the microencapsulation technique effectively protected xenografts of rat islets transplanted into diabetic mice. In a previous report, we described the success of allotransplanted microencapsulated rat islets in treating streptozotocin-induced diabetes in Wistar rats. We now report the in vitro study of human fetal islets microencapsulated within an alginate-polylysine membrane. A preliminary clinical trial of allotransplants for the treatment of insulin-dependent diabetics is also presented.

Adult↗