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Biomedical subjects

A Khan

Publications and source records attributed to A Khan.

At least 307 records · Page 17Linked to original sources
PubMed1997

Personality and depression: a validation study of the depressive experiences questionnaire.

This study investigated the validity of Blatt's model of depression as indicated by his operational measure of its constructs via the Depressive Experiences Questionnaire (DEQ; Blatt, D'Afflitti, & Quinlan, 1976). Hypothesized relations between the two relevant scales of the DEQ and Tellegen's (1982) Multidimensional Personality Questionnaire (MPQ) were examined. Participants consisted of 195 women, including 67 hospitalized unipolar depressives, 77 never-hospitalized unipolar depressives, and 51 nonpsychiatric controls. Overall, the results partially supported the validity of the DEQ even though all participants were women and prior studies have indicated the DEQ's greater discriminative validity for men than for women. However, several of the most strongly predicted relations, such as between DEQ Self-Criticism and MPQ Achievement were not confirmed. Coherent, significant relations between scales of the two measures remained after partialling out the effects of severity of depression.

Adolescent↗
PubMed1997

Pasteurella multocida infectious arthritis with acute gout after a cat bite.

A 74-year-old man with chronic lymphocytic leukemia, immune purpura, and gout presented with a painful, swollen ankle after a cat bite to his leg. On aspiration of the ankle, gram negative pleomorphic rods and monosodium urate crystals were seen and Pasteurella multocida was cultured. He was treated with ampicillin/sulbactam, joint aspiration, and intraarticular steroids, with resolution of infection and return of joint function. The syndromes of Pasteurella arthritis and crystal arthropathy with septic arthritis are reviewed.

Acute Disease↗
PubMed1997

Effect of experimental selenium deficiency and its supplementation on lymphoid organs.

Feeding of selenium deficient diet to albino rats for 75 days resulted in increased levels of plasma and adrenal glucocorticoids and atrophy of spleen and thymus. Supplementing the diet with selenium for 30 days resulted in recovery of atrophy of spleen and thymus; plasma and adrenal glucocorticoid levels were also restored back to the normal.

Animals↗
PubMed1996

Self-Assembly in a Mixture of Two Poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) Copolymers in Water

The self-assembly behavior in water of a mixture of two poly (ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) copolymers, (EO)13(PO)30(EO)13 (L64) and (EO)37(PO)58(EO)37 (P105), was explored at 25°C. The phase boundaries were established using 2H-NMR and inspection under polarized light; the structure of the various lyotropic liquid crystalline (LLC) phases was determined with small-angle X-ray scattering, while viscosity and differential scanning calorimetry measurements were used to probe the isotropic water-rich solution region. Isotropic regions, similar to the neat polymers, are stable at high polymer content. The addition of water induces structure in the amphiphilic block copolymer system. An extended lamellar (D) LLC phase is formed at 20-25% water content; a hexagonal (E) and a cubic (I) LLC phases supersede D at higher water contents. In addition to the above, a narrow isotropic region (L') is observed on the L64-water binary axis, in equilibrium with the E and the D phases. The hexagonal and lamellar LLC phases extended all the way from the L64-rich to the P105-rich side of the ternary L64-P105-water phase diagram; the characteristic hexagonal and lamellar structural dimensions varied linearly with P105 content in the L64-P105 mixture at a constant water concentration. An isotropic (micellar) solution phase (L1) dominates the high-water content corner of the ternary phase diagram. Viscosity measurements in this region provided evidence for increased interactions between the micelles as the boundary to the LLC phases was approached.

Journal Article↗
PubMed1996

Thymic dependence of loss of tolerance in mixed allogeneic bone marrow chimeras after depletion of donor antigen. Peripheral mechanisms do not contribute to maintenance of tolerance.

A nonmyeloablative conditioning regimen has recently been developed that allows allogeneic marrow engraftment with induction of permanent mixed chimerism and donor-specific tolerance across fully MHC-mismatched allogeneic barriers. We recently demonstrated that tolerance can be broken in these chimeras by administration of an anti-donor class I-specific monoclonal antibody that eliminates donor hematopoietic cells. We have now investigated the role of the thymus in the loss of tolerance observed when chimerism is eliminated in this manner. Mixed chimeras were prepared in B10 (H2b) recipients by treatment with depleting anti-CD4 and anti-CD8 mAbs, 3-Gy whole body irradiation, and 7-Gy thymic irradiation, followed by B10.A (H2a) bone marrow transplantation. Chimeras were thymectomized 7 weeks later, and were either untreated or were depleted of donor cells with anti-donor class I (Dd-specific) mAb 34-2-12. Control chimeras that were not thymectomized also received anti-donor monoclonal antibodies or no further treatment. Of the four groups, only euthymic animals that were depleted of donor antigen showed a loss of tolerance, as evidenced by rejection of B10.A skin grafts. In contrast to untreated control and thymectomized, anti-Dd-treated chimeras, these euthymic anti-Dd-treated chimeras showed significant recovery of Vbeta11+ T cells, which can recognize Mtv antigens presented by donor I-E molecules. The requirement for a thymus for loss of tolerance in the absence of donor antigen was verified in an adoptive transfer model, in which chimera (B10.A-->B10) spleen cells were depleted of donor-type cells ex vivo, adoptively transferred into B6 nu/nu mice, and then further depleted of donor-type antigen with monoclonal antibody treatment in vivo. These B6 nu/nu mice maintained donor-specific tolerance to B10.A skin grafts. The absence of active suppression as a potent mechanism of tolerance in long-term mixed chimeras was confirmed by the loss of mixed chimerism and of tolerance that was readily induced by injection of naive host-type spleen cells. Together, our results suggest that in mixed allogeneic chimeras, intrathymic clonal deletion, and not peripheral suppression or anergy, is the major mechanism maintaining donor-specific tolerance.

Animals↗
PubMed1996

Validation of the American Spinal Injury Association (ASIA) motor score and the National Acute Spinal Cord Injury Study (NASCIS) motor score.

STUDY DESIGN: In this study the motor scores of 62 consecutive acute spinal cord-injured patients were retrospectively reviewed. OBJECTIVE: The reliability of the American Spinal Injury Association and National Acute Spinal Cord Injury Study motor scores, compared with the conventional motor scores, was retrospectively assessed. SUMMARY OF BACKGROUND DATA: The reliability of the American Spinal Injury Association and National Acute Spinal Cord Injury Study scores has not as yet been confirmed. METHODS: Sixty-two consecutive adult patients admitted within 7 days of acute spinal cord injury between April, 1983, and September, 1992, were evaluated. The motor deficit percentage and the motor recovery percentage of each of the American Spinal Injury Association and the National Acute Spinal Cord Injury Study motor scores were compared with those of the conventional motor score. From the initial and final motor score, the motor deficit percentage and motor recovery percentage were calculated. There were 38 patients with cervical and thoracic lesions, 12 patients with dorso-lumbar lesions, and 12 patients with lower lumbar lesions. The average follow-up period was 41 months. RESULTS: Both the American Spinal Injury Association motor score and the National Acute Spinal Cord Injury Study motor score were representative of the conventional motor score for the evaluation of the motor deficit percentage and the motor recovery percentage in all levels (P < 0.0001). The differences in all correlation coefficients between the American Spinal Injury Association motor score and the National Acute Spinal Cord Injury Study motor score were not statistically significant in all levels and in every group. CONCLUSIONS: The American Spinal Injury Association and National Acute Spinal Cord Injury Study motor scores can both be used for the neurological quantification of motor deficit and motor recovery.

Adolescent↗
PubMed1996

Additional monoclonal antibody (mAB) injections can replace thymic irradiation to allow induction of mixed chimerism and tolerance in mice receiving bone marrow transplantation after conditioning with anti-T cell mABs and 3-Gy whole body irradiation.

While allogeneic bone marrow transplantation (BMT) has long been known to be capable of inducing donor-specific tolerance and hence permitting allograft acceptance without immunosuppressive pharmacotherapy, the toxicity of conditioning regimens required to achieve marrow engraftment has precluded the application of this approach to clinical organ transplantation. A relatively nontoxic method of conditioning mice that allows allogeneic bone marrow engraftment and induction of donor-specific skin allograft tolerance has recently been described. This regimen included anti-CD4 and anti-CD8 mAbs administered on day -5, followed by 3-Gy whole body irradiation (WBI) and 7-Gy thymic irradiation (TI) on day 0. To further reduce the potential toxicity of this regimen, we have now attempted to overcome the requirement for TI by administering additional mAb injections before and after BMT. Mixed chimerism and prolonged donor-specific skin graft acceptance were induced in 90% of B10 mice conditioned with anti-CD4 and -CD8 mAbs on days -6 and -1 and 3-Gy WBI on day 0 without TI. Despite long-term acceptance of donor-specific skin grafts, however, some of these animals showed a gradual decline in donor-type hematopoietic repopulation, and 2 of 10 mice regrafted with a second donor-type skin graft 5-9 months after BMT rejected the second and/or the original graft. This rejection after repeat donor-specific skin grafting correlated with a decline in the percentage of donor-type T cells between 6 and 12 weeks after BMT. In contrast, all animals receiving additional mAb injections 7 and 14 days following BMT after conditioning with mAbs on days -6 and -1 and 3-Gy WBI showed stable chimerism and accepted both primary and secondary donor-specific skin grafts. Animals receiving TI in addition to mAb and 3-Gy WBI also showed stable chimerism and long-term acceptance of initial (at 7 weeks) and later repeat donor-specific grafts. In contrast, the majority of mice receiving mAbs only on day -5 or on day -1 only, followed by 3-Gy WBI on day 0 without TI, did not accept initial donor-specific skin grafts, and showed only transient chimerism. Thus, the requirement for thymic irradiation to allow permanent mixed chimerism and donor-specific tolerance induction can be overcome by the administration of additional T cell-depleting mAb injections. These results establish a less toxic method of inducing donor-specific tolerance, thus increasing the potential clinical applicability of this approach to inducing organ allograft acceptance without chronic immunosuppressive therapy.

Animals↗
PubMed1996

Mechanism by which additional monoclonal antibody (mAB) injections overcome the requirement for thymic irradiation to achieve mixed chimerism in mice receiving bone marrow transplantation after conditioning with anti-T cell mABs and 3-Gy whole body irradiation.

A relatively nontoxic method of conditioning mice has been developed recently that allows allogeneic bone marrow engraftment and specific skin allograft tolerance induction. This regiment included anti-CD4 and anti-CD8 mAbs administered on day -5, followed by 3-Gy whole body irradiation (WBI) and 7-Gy thymic irradiation (TI) on day 0. We have recently shown that the potential toxicity of this regimen can be further reduced by replacing TI with additional anti-T cell mAb injections before and after bone marrow transplantation. Mixed chimerism and prolonged donor-specific skin graft acceptance are induced in 90% of B10 mice conditioned with anti-CD4 and anti-CD8 mAbs on days -6 and -1 and 3-Gy WBI on day 0 without TI, but only in a small fraction of mice receiving a similar regimen, except that mAbs are given on day -5 only. To determine the mechanism of tolerance induction in the former group, we compared the two groups for the extent of thymocyte depletion, for the timing of development of intrathymic and extrathymic chimerism, and for clonal deletion of host-type thymocytes with TCR recognizing superantigens presented by donor class II molecules. The results suggest that administration of a second mAb injection depletes or inactivates residual host thymocytes that are capable of causing intrathymic rejection of donor hematopoietic cells even when peripheral engraftment is achieved. The presence of donor class II+ hematopoietic cells in the thymus on day 14 correlated with marked deletion of mature host-type V beta 11+ thymocytes that recognize donor I-E plus endogenous superantigen. This suggests that tolerance is achieved primarily through a central deletional mechanism when peripheral and intrathymic host T cells are adequately inactivated or depleted by mAbs and 3-Gy WBI. In addition, the higher incidence of early failure of peripheral chimerism in mice conditioned with a single injection rather than than two mAb injections prior to bone marrow transplantation suggests that nontolerant residual host thymocytes can also induce early peripheral rejection after mAbs have cleared from the circulation. This early rejection is prevented by the longer persistence of anti-T cell mAbs observed in mice receiving two pretransplant mAb injections. Thus, administration of sufficient depleting anti-T cells mAbs followed by 3-Gy WBI allows the induction of central deletional tolerance while minimizing the toxicity of the conditioning regimen.

Animals↗
PubMed1996

Quantifying the carboxylation of pyruvate in pancreatic islets.

Pyruvate has been estimated to enter the citric acid cycle in islets by carboxylation to the same extent or more than by decarboxylation. Those estimates were made assuming the dimethyl esters of [1,4-14C]succinate and [2-3-14C]succinate, incubated with islets at a concentration of 10 mM, gave the same ratio of 14CO2 yields as if [1-14C]acetate and [2-14C]acetate had been incubated. The labeled succinates, at 10 mM, but not 1 mM, are now shown to give ratios higher than the labeled acetates at those concentrations and therefore higher estimates when related to yields from [2-14C]glucose and [6-14C]glucose. Using the labeled acetate ratios in paired incubations, the rate of pyruvate carboxylation is still estimated to be about two-thirds the rate of pyruvate decarboxylation. Participation of the malic enzyme-catalyzed reaction explains the greater ratio of yields of 14CO2 from the succinates at 10 mM than 1 mM and increases in those ratios on glucose addition and can account for the removal from the citric acid cycle of oxaloacetate carbon formed in the carboxylation.

Animals↗
PubMed1996

Effects of lipids on nucleotide inhibition of wheat-germ aspartate transcarbamoylase: evidence of an additional level of control?

Wheat-germ aspartate transcarbamoylase, a monofunctional trimer, is strongly inhibited by uridine 5'-monophosphate (UMP), which shows kinetic interactions with the substrate, carbamoyl phosphate, suggesting a classical allosteric mechanism of regulation. Inhibition of the purified enzyme by UMP was amplified in the presence of a variety of ionic lipids at concentrations low enough to preclude denaturation. In the absence of UMP, most of these compounds had no kinetic effect or were slightly activating. Two phospholipids did not show the effect. In a homologous series of fatty acids (C6-C16), the potentiating effect was only seen with homologues greater than C8, reaching a maximum at C12. The effect of dodecanoate (C12) on kinetic cooperativity (UMP as variable ligand) was studied. At each of several fixed concentrations of carbamoyl phosphate, dodecanoate had a pronounced effect on the half-saturating concentration of UMP, which was reduced by about half in every case, indicating substantially tighter binding of UMP. However, dodecanoate had relatively little effect on the kinetic Hill coefficient for the cooperativity of UMP. The possible metabolic significance of these effects is discussed.

Aspartate Carbamoyltransferase↗
PubMed1996

An evaluation of the antioxidant and antiviral action of extracts of rosemary and Provençal herbs.

Extracts of herbs and spices are increasingly of interest in the food industry because they retard oxidative degradation of lipids. There is also increasing interest in the antiviral activity of plant products. A liquid, deodorized rosemary extract and an oily extract of a mixture of Provençal herbs were tested for antioxidant and antiviral action in vitro. The rosemary extract (Herbor 025) and the extract of Provençal herbs (Spice Cocktail) inhibited peroxidation of phospholipid liposomes with 50% inhibition concentration values of 0.0009% (v/v) and 0.0035% (v/v), respectively. Herbor 025 and the spice cocktail (at 0.2%, v/v) reacted with trichloromethylperoxyl radical with calculated rates of 2.7 x 10(4) s-1 and 1.5 x 10(3) s-1, respectively. The main active components in the herbal preparations, carnosol and carnosic acid, at 0.05% (v/v) react with rate constants of (1-3) x 10(6) M-1 sec-1 and 2.7 x 10(7) M-1 sec-1, respectively. Both extracts show good antioxidant activity in the Rancimat test, especially in lard. Herbor 025 and the spice cocktail inhibited human immunodeficiency virus (HIV) infection at very low concentrations which were also cytotoxic. However, purified carnosol exhibited definite anti-HIV activity at a concentration (8 microM) which was not cytotoxic. Both preparations promoted some DNA damage in the copper-phenanthroline and the bleomycin-iron systems. The two herbal preparations possess antioxidant properties that may make them useful in the food matrix.

Abietanes↗
PubMed1996

Mechanical circulatory assistance in paediatric patients with cardiac failure.

Extracorporeal membrane oxygenation (ECMO) was initially developed for respiratory failure. Its use, however, has evolved into an excellent method of preoperative and postoperative support in the treatment of infants and children with acquired and congenital heart disease. Along with ECMO, the left ventricular assist device (LVAD) and the intraaortic balloon pump (IABP) have also found a place in the management of paediatric patients with heart failure. This report documents 15 patients who were treated with one or a combination of these mechanical devices, either preoperatively or postoperatively. There is a 74% survival rate and the long-term outcome has been excellent in most cases. The use of heparin-coated devices and tight regulation of heparin has allowed the transfer of infants and children from standard cardiopulmonary bypass to assist devices in the operating room. Mechanical devices are an essential adjunct for the preoperative and postoperative treatment of infants and children with cardiac disease.

Anticoagulants↗
PubMed1996

Immediate and long-term effect of mitral balloon valvotomy on left ventricular volume and systolic function in severe mitral stenosis.

To determine the immediate and long-term effect of mitral balloon valvotomy (MBV) on left ventricular (LV) volume and function, we studied 17 patients (mean age 27 +/- 9 years) with severe mitral stenosis undergoing MBV by cardiac catheterization and angiography before and immediately after MBV and at mean 12 months later. At baseline, LV end-diastolic volume index (EDVI) was reduced. Ten patients had EDVI < or = 55 ml/m2, and four patients (23.5%) had LV ejection fraction < 50%. EDVI increased from 60 +/- 17 ml/m2 to 66 +/- 17 ml/m2 (p < 0.05) immediately after MBV and increased further to 72 +/- 16 ml/m2 (p < 0.05) later. Stroke volume index increased from 34 +/- 10 ml/m2 to 41 +/- 12 ml/m2 (p < 0.05) immediately after MBV and increased further to 50 +/- 11 ml/m2 (p < 0.001) later. LV end diastolic pressure increased from 12 +/- 5 mm HG to 16 +/- 4 mm HG (p < 0.05) immediately after MBV and fell to 13 +/- Hg at follow-up. LV ejection fraction increased from 57 +/- 7% to 62 +/- 6% (p < 0.05) immediately after MBV and 71 +/- 8% later (p < 0.001). Mean systolic ejection rate increased from 82 +/- 35 ml/sec to 101 +/- 48 ml/sec (p < 0.05) immediately after and 165 +/- 81 ml/sec later (p < 0.05). Systemic vascular resistance fell from 1887 +/- 525 dyne/sec/cm-5 to 1280 +/- 231 dyne/sec/cm-5 (p < 0.001) at follow-up. We conclude that the LV end-diastolic volume and systolic function are reduced in patients with mitral stenosis, and the LV end-diastolic volume is increased immediately after MBV and continues to increase at follow-up 12 months later; the LV ejection performance improves after successful MBV because of an increase in end-diastolic LV volume (preload) and reduction of SVR.

Adolescent↗
PubMed1996

Front-line management of pulmonary tuberculosis: an analysis of tuberculosis and treatment practices in urban Sindh, Pakistan.

SETTING: Karachi and Hyderabad, Pakistan. OBJECTIVE: To describe the level and quality of tuberculosis (TB) case management by non-TB control program (TCP) physicians in urban Sindh, Pakistan. DESIGN: We interviewed 152 adults with pulmonary TB confirmed by Karachi's TB control program regarding the initial management of their TB symptoms before entering the TCP. We also surveyed 65 general practitioners (GPs) attending continuing education seminars with a multiple choice test to assess their management of suspected pulmonary TB. We compared both results to guidelines from the World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD). RESULTS: Eighty percent (122/152) of patients first sought GPs. Only 14% of GPs performed any sputum test. At most, 17 (40%) of the 42 patients recalling their GP's treatment, received the recommended 4-drug regimen. However, 68% (45/65) of surveyed GPs chose correct treatment from a multiple choice format. But their initial laboratory investigations, follow-up, and treatment cessation criteria (9%, 9-31%, and 11% correct, respectively) demonstrated under-utilization of sputum tests and over-reliance on unhelpful tests. CONCLUSIONS: GPs first saw most of these TCP patients, but their weak management likely hinders TB control. A partnership between TB control programs and GPs could improve case management and hasten TB control.

Adolescent↗
PubMed1996

Polarity of T cell shape, motility, and sensitivity to antigen.

T cell activation requires contact with APCs. We used optical techniques to demonstrate T cell polarity on the basis of shape, motility, and localized sensitivity to antigen. An intracellular Ca2+ clamp showed that T cell shape and motility are extremely sensitive to changes in [Ca2+]i (Kd = 200 nM), with immobilization and rounding occurring via a calcineurin-independent pathway. Ca2+ dependent immobilization prolonged T cell contact with the antigen-presenting B cell; buffering the [Ca2+]i signal prevented the formation of stable cell pairs. Optical tweezers revealed spatial T cell sensitivity to antigen by controlling placement on the T cell surface of either B cells or alpha-CD3 MAb-coated beads. T cells were 4-fold more sensitive to contact made at the leading edge of the T cell compared with the tail. We conclude that motile T cells are polarized antigen sensors that respond physically to [Ca2+]i signals to stabilize their interaction with APCs.

Animals↗
PubMed1996

The care of older persons with diabetes mellitus: families and primary care physicians.

OBJECTIVES: To determine the extent to which family members participate in the day-to-day management of diabetes mellitus in older persons, and in older diabetics' medical encounters, and to identify patient and family member characteristics associated with this participation. DESIGN: A longitudinal observational study, with baseline data being reported herein. SETTING: Three primary care practice settings in Seattle, Washington, Boston, Massachusetts, and Indianapolis, Indiana. PARTICIPANTS: Family members of patients 70 years of age or older participating in the Patient Outcomes Research Team (PORT) Study of type II diabetics. MAIN OUTCOME MEASUREMENTS: The two dependent variables represent, respectively, the extent of family members' assistance with diabetes-related care and participation in older diabetics' medical encounters. RESULTS: The 357 family members enrolled were older (mean age = 66.3 years), were mostly women (76.2%), and were usually the spouses of diabetic patients (71.3%). Between 22% and 50% of family members reported helping with various aspects of diabetes care; 35.6% of family members participated regularly in their diabetic patients' medical encounters. A multiple linear regression model relating family assistance with diabetes-related care to patient and family member characteristics included four variables: patients' physical function, and the family member's relationship to the patient, assistance with basic activities of daily living (ADLs), and understanding of diabetes management issues (all P < .05). A multiple logistic regression model relating family member participation in the medical encounter to patient and family member characteristics also included four variables: patient age and physical function, and family member assistance with instrumental activities of daily living (IADLs) and with diabetes-related care (all P < .05). CONCLUSION: The family members studied frequently assisted older diabetics with diabetes-specific care; more than one-third were regular participants in older diabetics' medical encounters. Family member involvement in the day-to-day management of diabetes and in the medical encounter was more likely when patients were functionally disabled. Health care systems and physicians need to educate their older patients, and involved family members when patients are frail, about diabetes-related care issues and support them in their roles in the management of diabetes as well as other chronic diseases.

Activities of Daily Living↗
PubMed1996

Impaired coupling of glucose signal to the exocytotic machinery in diabetic GK rats: a defect ameliorated by cAMP.

The GK rat is a spontaneous model of NIDDM. The insulin response to 16.7 mmol/l glucose was markedly impaired in both isolated perfused pancreas and isolated islets from GK rats compared with control Wistar rats. Depolarization with 30 mmol/l KCl in the presence of 3.3 mmol/l glucose and 250 micromol/l diazoxide induced similar insulin responses in perfused pancreases of GK and control rats. In contrast, the glucose-stimulated insulin release was also severely impaired in GK pancreases in the depolarized state. Forskolin (1 micromol/l) markedly enhanced insulin release at 3.3 mmol/l glucose in GK but not control pancreases (54 +/- 15 vs. 3 +/- 1 pmol/10 min, P < 0.001). Dibutyryl cAMP (1 mmol/l) exerted effects similar to forskolin on insulin release in the perfused pancreas. In depolarized pancreases of GK but not control rats, forskolin also induced a marked insulin response at 3.3 mmol/l glucose (163 +/- 48 vs. 16 +/- 1 pmol/20 min, P < 0.03). Similarly, in studies on isolated islets from GK rats cultured in 5.5 or 16.7 mmol/l glucose for 48 h, forskolin (5 pmol/l) restored insulin release in response to 16.7 mmol/l glucose but had no effect on islet glucose utilization at 3.3 or 16.7 mmol/l glucose. Forskolin markedly stimulated insulin release at 3.3 mmol/l glucose in GK but not control rat islets cultured for 48 h in 5.5 mmol/l glucose, whereas 20 mmol/l arginine had an almost identical effect in both islet varieties. However, in islets cultured in 16.7 mmol/l glucose, forskolin stimulated insulin release similarly both in control and GK islets at 3.3 mmol/l glucose. In conclusion, this study suggests that the insulinotropic effects of glucose are coupled to a direct regulation of the exocytotic machinery in the pancreatic beta-cell. This pathway is markedly impaired in GK rats, contributing to defective insulin response to glucose. In this model, cAMP generation restores the insulin response to 16.7 mmol/l glucose and exerts a marked insulin release even at 3.3 mmol/l glucose.

Animals↗