Glucose-Stimulated 45Calcium Efflux from Isolated Rat Pancreatic Islets

Kinetics of (45)Ca efflux and insulin release were studied in collagenase-isolated rat islets during 2-h perifusions with calcium-depleted (0.05 mM) bicarbonate-phosphate buffer containing 2.2 mM glucose. Addition of glucose (16.7 mM) suppressed (45)Ca efflux by 30%. Removal of glucose caused an "off response" of insulin release. The perifusion of a normal concentration of Ca (2.3 mM) greatly stimulated (45)Ca efflux, indicating Ca <--> (45)Ca exchange. When Ca and glucose were superimposed, the effects on (45)Ca efflux and insulin release depended upon the order of presentation of the stimuli: when Ca was added to an ongoing 16.7-mM glucose perifusion, biphasic patterns of (45)Ca and insulin release were seen; when glucose was superimposed on a Ca perifusion, an inhibition of the Ca-stimulated (45)Ca efflux occurred, and a reduced but clearly biphasic insulin response was seen. The subsequent insulin off response after with-drawal of the glucose was also reduced.Mathematical "peeling" of (45)Ca efflux curves from unstimulated islets suggests that there are at least two, and probably three, different intracellular Ca compartments (not including the extracellular sucrose space). At the beginning of perifusion, these three compartments (I, II, III) contain 25, 56, and 19% of the intracellular (45)Ca, and their rates of efflux are 6.7, 1.2, and 0.1%/min, respectively. Glucose appears to suppress efflux from the largest compartment (II); Ca appears to exchange with (45)Ca from a more inert compartment (III). The relationship between insulin and (45)Ca release is not stoichiometric.     

Evidence for the Involvement of Na/Ca Exchange in Glucose-induced Insulin Release from Rat Pancreatic Islets

Glucose-induced inhibition of Ca⁺⁺ extrusion from the β-cell may contribute to the rise in cytosol Ca⁺⁺ that leads to insulin release. To study whether interference with Na/Ca exchange is involved in this inhibition the effects of glucose were compared to those of ouabain. This substance inhibits Na/K ATPase, decreases the transmembrane Na⁺ gradient in islets, and thus interferes with Na/Ca exchange. Collagenase isolated rat islets were maintained for 2 d in tissue culture with a trace amount of ⁴⁵Ca⁺⁺. Insulin release and ⁴⁵Ca⁺⁺ efflux were then measured during perifusion. In Ca⁺⁺-deprived medium (to avoid changes in tissue specific radioactivity) 16.7 mM glucose inhibited ⁴⁵Ca⁺⁺ efflux. Initially 1 mM ouabain inhibited ⁴⁵Ca⁺⁺ efflux in a similar fashion, the onset being even faster than that of glucose. The effects of 16.7 mM glucose and ouabain were not additive, indicating that both substances may interfere with Na/Ca exchange. In the presence of Ca⁺⁺, 16.7 mM glucose induced biphasic insulin release. Ouabain alone caused a gradual increase of insulin release. Again, the effects of ouabain and 16.7 mM glucose were not additive. In contrast, at a submaximal glucose concentration (7 mM) ouabain enhanced both phases of release. An important role for Na/Ca exchange is suggested from experiments in which Ca⁺⁺ was removed at the time of glucose-stimulation (16.7 mM). The resulting marked inhibition of insulin release was completely overcome during first phase by ouabain added at the time of Ca⁺⁺ removal; second phase was restored to 60%. This could be due to the rapid inhibitory action of ouabain on Ca⁺⁺ efflux thereby preventing loss of cellular calcium critical for glucose to induce insulin release. It appears, therefore, that interference with Na/Ca exchange is an important event in the stimulation of insulin release by glucose.     

Insulin and Glucagon Secretion by Pancreatic Islets from Nondiabetic and Diabetic Sand Rats (Psammomys obesus)

Abstract. The secretion of insulin and glucagon was investigated in pancreatic islets from diabetic and nondiabetic sand rats of similar age and weight. The metabolic characterization was based on an intraperitoneal glucose tolerance test. Compared to nondiabetic animals diabetic sarid rats had a diminished insulin content in their islets and a decreased insulin secretory response to glucose, glyceraldehyde and theophylline. Diazoxide inhibited insulin release in diabetic as well as in nondiabetic sand rats whereas mannoheptulose was effective only in the nondiabetic rats. There was no significant difference in glucagon content between the two groups. The glucagon secretion by pancreatic islets of diabetic animals was not suppressed by glucose, as in nondiabetic sand rats islets, but by glyceraldehyde. This indicates that the sensitivity to glucose rather than the suppressibility of glucagon release was altered.     

Isolation and Characterization of Immunoreactive Somatostatin from Fish Pancreatic Islets

Using a radioimmunoassay with labeled synthetic tetradecapeptide somatostatin, a large amount of immunoreactive somatostatin was found in the principal pancreatic islet of the channel catfish (Ictalurus punctata). The purpose of these experiments was to isolate and characterize the somatostatin-like material. Extracts of islets were chromatographed on a Bio-Gel P-30 column, and over 90% of the immunoreactive somatostatin migrated with proteins at least twice the size of synthetic tetradecapeptide somatostatin. This fraction was further purified by ion-exchange chromatography on carboxymethyl-cellulose and DEAE-cellulose columns. Two peptides were obtained with identical immunoreactivity, which was approximately 25% that of the synthetic somatostatin. Each peptide was judged to be >95% pure by thin-layer electrophoresis, polyacrylamide gel electrophoresis at pH 8.9, and highpressure liquid chromatography. Further criteria of purity included amino-terminal analysis of fraction IV yielding only aspartic acid. A total of 1.3 mg of fraction II, and 3.8 mg of fraction IV somatostatin-like peptides were obtained from 10 g of fresh frozen islets.Characterization of the two peptides revealed both peptides slightly more acidic than synthetic tetradecapeptide somatostatin. Fraction II had an isoelectric point of 8.0-8.3, and fraction IV 8.3-9.0. Molecular weight estimation by sodium dodecyl sulfate-urea polyacrylamide gel electrophoresis revealed similar mobility of both peptides, between pancreatic polypeptide (mol wt 4,500) and glucagon (mol wt 3,500). The mobility was not altered by reduction, and was approximately twice the size of synthetic tetradecapeptide somatostatin (mol wt 1,800). This confirmed that the peptides were single polypeptide chains and not aggregates, or somatostatin bound to larger proteins. Molecular weight determination by gel filtration chromatography on Bio-Gel P-6 in 8 M urea gave an estimated mol wt of 3,700. Amino acid analysis of the two immunoreactive somatostatins indicated that they were very similar in composition. Both pancreatic somatostatins (1 muM) had full biological activity relative to synthetic somatostatin measured as inhibition of growth hormone release from rat anterior pituitary cells.     

Interacting Effects of Sulfonylureas and Glucose on Cyclic AMP Metabolism and Insulin Release in Pancreatic Islets of the Rat

The effects of tolbutamide and glibenclamide on the metabolism of cyclic AMP were investigated in pancreatic islets of the rat. Changes in cyclic AMP were assessed by measuring [(3)H]cyclic AMP after labeling of the islets with [2-(3)H]adenine. In the presence of a nonstimulatory concentration of glucose (3.3 mM), both sulfonylureas caused a rapid increase in islet [(3)H]cyclic AMP, which declined within 5 (tolbutamide) or 10 min (glibenclamide). In the absence of glucose, the glibenclamide effect was shortened, but the initial (1 min) response of [(3)H]-cyclic AMP was unaffected. Glucose could be substituted with d-glyceraldehyde but not pyruvate for prolongation of the glibenclamide response. The effect of glucose withdrawal on the glibenclamide response was reproduced by the addition of d-mannoheptulose to glucose containing media.The [(3)H]cyclic AMP response to glibenclamide was influenced by prior exposure of the islets to glucose, a 30-min preincubation with 27.7 mM glucose, enhancing the response to the sulfonylurea over a subsequent 5-min stimulation period.Sulfonylureas exerted their effects at low but not at high glucose concentrations, i.e., shifted the glucose dose-response curve to the left both for [(3)H]cyclic AMP accumulation and insulin release. On the other hand, increasing concentrations of the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, progressively augmented the effects of the drugs.Omission of Ca(++) from the incubation media inhibited both the glucose and the sulfonylurea [(3)H]-cyclic AMP and insulin responses. Epinephrine (1 muM) partially inhibited the [(3)H]cyclic AMP response to both glucose and sulfonylurea, whereas insulin release was completely abolished.It is concluded that the sulfonylurea effects on islet cyclic AMP are intimately related to those of glucose. It is suggested that sulfonylureas exert a major part of their action by facilitating the effect of glucose on the beta-cell adenylate cyclase; the increased cyclic AMP level, in its turn, enhances the secretion rate of insulin.     

Somatostatin- and Epinephrine-Induced Modifications of 45Ca++ Fluxes and Insulin Release in Rat Pancreatic Islets Maintained in Tissue Culture

The effects of somatostatin and epinephrine have been studied with regard to glucose-induced insulin release and (45)Ca(++) uptake by rat pancreatic islets after 2 days in tissue culture and with regard to (45)Ca(++) efflux from islets loaded with the radio-isotope during the 2 days of culture. (45)Ca(++) uptake, measured simultaneously with insulin release, was linear with time for 5 min. (45)Ca(++) efflux and insulin release were also measured simultaneously from perifused islets.Glucose (16.7 mM) markedly stimulated insulin release and (45)Ca(++) uptake. Somatostatin inhibited the stimulation of insulin release by glucose in a concentration-related manner (1-1,000 ng/ml) but was without effect on the glucose-induced stimulation of (45)Ca(++) uptake. Similarly, under perifusion conditions, both phases of insulin release were inhibited by somatostatin while no effect was observed on the pattern of (45)Ca(++) efflux after glucose.Epinephrine, in contrast to somatostatin, caused a concentration-dependent inhibition of the stimulation of both insulin release and (45)Ca(++) uptake by glucose. Both phases of insulin release were inhibited by epinephrine and marked inhibition could be observed with no change in the characteristic glucose-evoked pattern of (45)Ca(++) efflux (e.g., with 10 nM epinephrine). The inhibitory effect of epinephrine on (45)Ca(++) uptake and insulin release appeared to be mediated via an alpha-adrenergic mechanism, since is was abolished in the presence of phentolamine.Somatostatin inhibits insulin release without any detectable effect upon the handling of calcium by the islets. In contrast, inhibition of insulin release by epinephrine is accompanied by a partial inhibition of glucose-induced Ca(++) uptake.     

Ultrasound Stimulation of Insulin Release from Pancreatic Beta Cells as a Potential Novel Treatment for Type 2 Diabetes

Type 2 diabetes mellitus is a complex metabolic disease that has reached epidemic proportions in the United States and around the world. This disease is characterized by loss of insulin secretion and, eventually, destruction of insulin-producing pancreatic beta cells. Controlling type 2 diabetes is often difficult as pharmacological management routinely requires complex therapy with multiple medications, and loses its effectiveness over time. The objective of this study was to explore the effectiveness of a novel, non-pharmacological approach that uses the application of ultrasound energy to augment insulin release from rat INS 832/13 beta cells. The cells were exposed to unfocused ultrasound for 5 min at a peak intensity of 1 W/cm² and frequencies of 400 kHz, 600 kHz, 800 kHz and 1 MHz. Insulin release was measured with enzyme-linked immunosorbent assay and cell viability was assessed via the trypan blue dye exclusion test. A marked release (approximately 150 ng/10⁶ cells, p < 0.05) of insulin was observed when beta cells were exposed to ultrasound at 400 and 600 kHz as compared with their initial control values; however, this release was accompanied by a substantial loss in cell viability. Ultrasound application at frequencies of 800 kHz resulted in 24 ng/10⁶ cells released insulin (p < 0.05) as compared with its unstimulated base level, while retaining cell viability. Insulin release from beta cells caused by application of 800-kHz ultrasound was comparable to that reported by the secretagogue glucose, thus operating within physiological secretory capacity of these cells. Ultrasound has potential as a novel and alternative method to current approaches aimed at correcting secretory deficiencies in patients with type 2 diabetes.     

(Pro-)Insulin Biosynthesis and Release of Newly Synthesized (Pro-)Insulin from Isolated Islets of Rat Pancreas in the Presence of Amino Acids and Sulphonylureas+,++

Abstract. The influence of arginine, lysine, tolbutamide and glibenclamide on (pro-)insulin biosynthesis and release of newly synthesized (pro-)insulin was studied in isolated islets of rat pancreas. Islets were incubated with ³H-leucine and glucose in the presence and absence of the test agents. Proinsulin and insulin of islets and incubation media were separated by gel filtration on Sephadex G 50. Estimations were carried out for radioactivity and immunoreactivity for insulin. All four test substances were able to enhance insulin release whereas no stimulation of leucine incorporation into (pro-)insulin was found. Arginine and tolbutamide even markedly reduced (pro-)insulin synthesis. Conversion of proinsulin to insulin was not affected by any of the test agents. For studying the influence of the 4 substances on secretion of newly synthesized (pro-)insulin two experimental models were used: 1) Labelling of the islets in the presence of the test agents, followed by uniform stimulation with glucose alone in the presence or absence of Ca⁺⁺. 2) Addition of the 4 test substances after uniform prelabelling of the islets. 1) Presence of arginine and sulfonylureas during labelling resulted in a significantly enhanced relative fractional release of newly synthesized (pro-)insulin, although the bulk of secreted hormone appeared to stem from the storage pool also under these conditions. The enhanced fractional release was persistent also during the postlabelling period when the islets had been labelled in the presence of arginine or glibenclamide. On the other hand, a decreased release of newly synthesized (pro-)insulin was observed during the postlabelling period in islets labelled in the presence of tolbutamide. Lysine was without significant effects in both periods. Omission of calcium ions during the postlabelling period inhibited the release of both immunoreactive and radioactive hormone. 2) When amino acids or sulphonylureas were added after prelabelling no signifcant changes were found in the specific radioactivity of released (pro-)insulin or in the fractional release of newly synthesized hormone. Enhanced release of fresh granules from the beta cell might explain the increased fractional release of newly synthesized (pro-) insulin when labelling is carried out in the presence of arginine and sulphonylureas, especially glibenclamide.     

(Pro-)Insulin Biosynthesis and Release of Newly Synthesized (Pro-)Insulin from Isolated Islets of Rat Pancreas in the Presence of Amino Acids and Sulphonylureas+,++

Abstract. The influence of arginine, lysine, tolbutamide and glibenclamide on (pro-)insulin biosynthesis and release of newly synthesized (pro-)insulin was studied in isolated islets of rat pancreas. Islets were incubated with ³H-leucine and glucose in the presence and absence of the test agents. Proinsulin and insulin of islets and incubation media were separated by gel filtration on Sephadex G 50. Estimations were carried out for radioactivity and immunoreactivity for insulin. All four test substances were able to enhance insulin release whereas no stimulation of leucine incorporation into (pro-)insulin was found. Arginine and tolbutamide even markedly reduced (pro-)insulin synthesis. Conversion of proinsulin to insulin was not affected by any of the test agents. For studying the influence of the 4 substances on secretion of newly synthesized (pro-)insulin two experimental models were used: 1) Labelling of the islets in the presence of the test agents, followed by uniform stimulation with glucose alone in the presence or absence of Ca⁺⁺. 2) Addition of the 4 test substances after uniform prelabelling of the islets. 1) Presence of arginine and sulfonylureas during labelling resulted in a significantly enhanced relative fractional release of newly synthesized (pro-)insulin, although the bulk of secreted hormone appeared to stem from the storage pool also under these conditions. The enhanced fractional release was persistent also during the postlabelling period when the islets had been labelled in the presence of arginine or glibenclamide. On the other hand, a decreased release of newly synthesized (pro-)insulin was observed during the postlabelling period in islets labelled in the presence of tolbutamide. Lysine was without significant effects in both periods. Omission of calcium ions during the postlabelling period inhibited the release of both immunoreactive and radioactive hormone. 2) When amino acids or sulphonylureas were added after prelabelling no signifcant changes were found in the specific radioactivity of released (pro-)insulin or in the fractional release of newly synthesized hormone. Enhanced release of fresh granules from the beta cell might explain the increased fractional release of newly synthesized (pro-) insulin when labelling is carried out in the presence of arginine and sulphonylureas, especially glibenclamide.     

Blunt Pancreatic Head Hematoma as an Infrequent Cause of Delayed Obstructive Jaundice

Background

Blunt pancreatic injury is a rare type of abdominal trauma. It is a challenge to physicians due to difficulties in early diagnosis and associated complications. Most simple cases of pancreas contusion and hematoma can be safely treated conservatively. Nevertheless, the possibility of delayed mass effect and complications always exists.

Objectives

We present a case with delayed complications after blunt pancreatic trauma.

Case Report

A 70-year-old woman with simple pancreatic head hematoma was treated conservatively. A delayed obstructive jaundice occurred 4 weeks subsequent to the trauma. Endoscopic retrograde cholangiopancreatography (ERCP) with biliary stent placement provided a successful treatment instead of surgical intervention.

Conclusion

A pancreatic hematoma after blunt abdominal trauma can be complicated by common bile duct obstruction with a delayed onset of obstructive jaundice. The application of ERCP with placement of a biliary stent was effective in this case. Conscientious follow-up and serial imaging studies should be utilized in patients with an initial presentation of an uncomplicated pancreatic head hematoma.     

Phosphorus Release from Rock Phosphate as Influenced by Organic Acid Loaded Nanoclay Polymer Composites in an Alfisol

The aim of the present study was to develop a strategy to solubilize low-grade rock phosphate (RP) from Purulia and Udaipur through organic acids loaded nanoclay polymer composites (NCPC) and see their effectiveness as source of P. An incubation experiment was conducted under laboratory condition to study the release pattern of P in an Alfisol from Jharkhand amended with various RPs treated with organic acid loaded NCPC for 90 days. The RPs were applied at a dose of 0, 50 and 100 mg P kg^?1 soil, along with the organic acid loaded NCPC having 10 % clay which was applied at a dose of 0, 20 and 40 mg organic acid kg^?1 soil. The incubation experiment showed a positive impact of the organic acids in their ability to release P from all the RP sources, and oxalic acid performed better over citric acid in solubilizing P from RPs. The two indigenous RPs maintained almost comparable available P in soil throughout the period of incubation. With increase in levels of P application, there was an increase in the amount of release of P from both the RPs. Similarly, with the increase in levels of organic acid both Udaipur and Purulia RPs showed increase in the available P in soil. This study demonstrated that availability of P from low-grade indigenous RP could be improved with the interventions of organic acid loaded NCPC which could be used as P-fertilizer and reduce the dependence on commercial fertilizers like DAP.     

Insulin Sensitivity as an Independent Predictor of Fat Mass Gain in Hispanic Adolescents

OBJECTIVE

The purpose of this study was to examine the relationship between changes in insulin sensitivity and subsequent changes in fat mass in obese Hispanic children over 3 consecutive years.

RESEARCH DESIGN AND METHODS

In a longitudinal research design, insulin sensitivity (S_i) of 96 research participants was determined at baseline and 1 year later. Body adiposity was assessed at four assessments.

RESULTS

The change in S_i during the first year of the study was a significant predictor of further fat mass development (P < 0.05). Considering different directions of S_i change, S_i was a strong predictor for further fat mass development only in the group that decreased their S_i (P < 0.05).

CONCLUSIONS

The results show that the direction of change in insulin sensitivity at an early age is an important independent predictor for further fat mass development and emphasize the importance of insulin sensitivity as a primary target for long-term obesity prevention, as well as the significance of early age intervention.Hispanic youth are disproportionately affected by the pediatric obesity epidemic and the associated comorbidities such as type 2 diabetes (1). Although the pathogenesis of type 2 diabetes in children remains unclear, it likely involves characteristics similar to those of adults (2), including the negative effect of increased adiposity on insulin sensitivity and subsequent β-cell failure (3,4). While insulin resistance traditionally has been examined as a consequence of increased adiposity, there is evidence that insulin resistance at an early age in turn may increase adiposity in adolescents and early adulthood (5). The purpose of this study is to further clarify whether changes in insulin resistance early in life are related to fat mass development later in life in Hispanic adolescents.     

Immediate and Time-Dependent Effects of Glucose on Insulin Release from Rat Pancreatic Tissue: EVIDENCE FOR DIFFERENT MECHANISMS OF ACTION

Glucose-induced insulin secretion is enhanced by a preceeding glucose stimulus. The characteristics of this action of glucose were investigated in perfused pancreas and collagenase-isolated islets of Langerhans. A 20- to 30-min pulse of 27.7 mM glucose enhanced both the first and second phase of insulin release in response to a second glucose stimulus by 76-201%. This enhancement was apparent as an augmented maximal insulin release response to glucose. The effect of priming with glucose was seen irrespective of whether the pancreatic tissue was obtained from fed or fasted rats. Separating the two pulses of hexose by a 60-min time interval of exposure to 3.3 mM glucose did not abolish the potentiation of the second pulse. Omission of Ca(++) as well as the inclusion of somatostatin or mannoheptulose during the first pulse abolished insulin secretion during this time period; however, only the inclusion of mannoheptulose deleted the potentiation of the second pulse. d-Glyceraldehyde, but not pyruvate, d-galactose, or 3-isobutyl-1-methylxanthine, could substitute for glucose in inducing potentiation.In islets labeled with [2-(3)H]adenine, the [(3)H]cyclic AMP response to glucose was increased by 35% when measured after 1 min, but was increased only marginally after 2-10 min of stimulation with a second pulse of glucose. The production of (3)H(2)O from glucose was not affected by glucose priming.It is concluded that (a) the induction of the glucose-induced, time-dependent potentiation described here is dependent on glucose metabolism but not on stimulation of cyclic AMP, calcium fluxes, or insulin release per se; (b) the mechanisms that mediate the pancreatic "memory" for glucose are unknown but do not seem to involve to a major extent an increased activity of the adenylate cyclase-cyclic AMP system of the beta-cell; (c) the evidence presented supports the hypothesis of a dual role of glucose for insulin release.     

Early identification of leptospirosis as an ignored cause of multiple organ dysfunction syndrome

Leptospirosis is the most common zoonosis in the world but remains underreported, owing to protean manifestations and ignorance about the disease among health care providers in Taiwan. From September 2000 to March 2006, surveillance of 455 patients with multiple organ dysfunction syndrome with unclear cause or clinical suspicion of leptospirosis was performed. Diagnosis was further confirmed by microscopic agglutination test or isolation of Leptospira. Cases were classified as excluded based on confirmed etiology other than leptospirosis or negative paired serologic test. Forty-two patients were confirmed as having leptospirosis, which accounted for 9.2% of total patients with multiple organ dysfunction syndrome. Forty-nine excluded cases were identified for a case-control analysis for clinical distinction. The most common presentations of leptospirosis were fever (97.6%), acute kidney injury (85.7%), and jaundice (61.9%). The leptospirosis group showed lower urine specific gravity (cutoff value, 1.0145) and enlarged kidney size (cutoff value, 11.05 cm) as compared with the excluded cases by multivariate logistics regression. Delayed antibiotic administration prolongs the duration of hospitalization (R2 = 0.486, P < 0.01). No mortality has been found in the leptospirosis group after initiation in 2003 of rapid immunoglobulin M serology assay that showed considerably high sensitivity and specificity. Leptospirosis accounts for a salient cause of multiple organ dysfunctions in Taiwan. Early awareness of leptospirosis by distinct presentations, followed by prompt antibiotics therapy, can dramatically save the patients. The easily performed rapid immunoglobulin M serology assay is suitable as a rapid screening test for the diagnosis of leptospirosis.     

Fever and Psychosis as an Early Presentation of Brucella-Associated Meningoencephalitis: A Case Report

Objective

To describe a case with Brucella-associated meningoencephalitis. In addition, we report drug-induced hepatotoxicity due to acyclovir.

Clinical Presentation and Intervention

A young woman was admitted with fever and psychosis and neuroimaging findings indicative of meningoencephalitis. Serology was positive for Brucella. She was treated with doxycycline, rifampin, and trimethoprim-sulfamethoxazole.

Conclusion

This case reminds physicians in endemic regions to consider neurobrucellosis as a differential diagnosis in patients with any unexplained neurologic symptoms or atypical psychosis. Early diagnosis and treatment of neurobrucellosis will be helpful in decreasing the sequelae of this complication.Key Words: Brucellosis, Meningoencephalitis, Psychosis, Acyclovir, Hepatotoxicity     

Insulin B chain functions as an effective competitor of antigen presentation via peptide homologies present in the thymus

The B chain of mammalian insulins contains appropriately spaced amino acids that predict recognition by T cells. However, all T cell clones from an HLA-DR1, Dw6 diabetic donor recognize epitopes associated with the A chain, and the B chain was found to inhibit these responses. Effective intramolecular competition at the level of the APC, not a direct effect on the T cell, is responsible for the inhibition. Insulin B chain contains two clusters of amino acid homology with the TCR beta chain and B chain peptides lacking these clusters do not compete for antigen presentation. A hole in the repertoire for T cells that recognize this portion of the insulin molecule may arise in the thymus by deletion of T cells that recognize similar peptides.     

Early diastolic motion of the posterior aortic root as an index of left ventricular filling

Aortic root motion on M-mode echocardiography is related to left atrial volume change. Early diastolic motion of the aortic root has been quantified by the atrial emptying index. This index has been shown by some investigators to assess early diastolic left ventricular filling, while other investigators report conflicting findings. To evaluate further early diastolic motion of the posterior aortic root, we describe a new echocardiographic parameter—the slope of early diastolic posterior aortic root motion. This parameter appears superior to the atrial emptying index in assessing early diastolic left ventricular filling. Forty-one patients were studied by M-mode echocardiography and were divided into group I (17 patients) with diminished E to F mitral value slopes (<70 mm/sec) and group II (24 patients) with normal E to F mitral valve slopes (≥70 mm/sec). Patients in group I and group II had comparable left atrial sizes and left ventricular dimensions. The aortic root slope and normalized aortic root slope (normalized for left atrial dimension) in group I (3.7 ± 1.4 cm/sec and 1.0 ± 0.4 sec^?1, respectively) were significantly less than in group II (6.4 ± 1.4 cm/sec and 1.9 ± 0.6 sec^?1, respectively). The atrial emptying index and atrial emptying index normalized for heart rate were not different between the two groups. When the 41 patients were analyzed according to the presence or absence of left ventricular hypertrophy by echocardiography, only the normalized aortic root slope was significantly different in patients with or without left ventricular hypertrophy. A significant linear correlation (r = 0.84, P < 0.0005) was found between the aortic root slope or normalized aortic root slope and the E to F slope of the mitral valve. Significant correlations also existed between the aortic root slope and the slope of early diastolic left ventricular rapid filling. Therefore, the slope of early diastolic motion of the posterior aortic root appears to be a useful and easily obtainable echocardiographic parameter to assess early diastolic left ventricular filling.