RESUMO
To test the hypothesis that FSH is secreted at least in part within discrete secretory bursts in women and that the characteristics of episodic FSH secretion are altered within differing gonadal hormone environments, we measured FSH by immunoradiometric assay every 10 min for 24 h in premenopausal women during the early follicular (EF), late follicular (LF), and midluteal (ML) phases of the menstrual cycle and in postmenopausal (PM) women (n = 8 in each group). Secretory events were evaluated using multiparameter deconvolution. FSH was secreted in an episodic manner, with the number of secretory bursts (per 24 h; mean +/- SEM) detected in LF (20 +/- 0.79) and PM (20 +/- 0.90) women being greater than that in EF (16 +/- 0.88) and ML (14 +/- 0.93) women. FSH secretory burst mass (milliinternational units per mL) was significantly higher in PM (12 +/- 1.6) than in EF (1.8 +/- 0.21), LF (3.1 +/- 1.3), or ML (0.8 +/- 0.11) women and primarily reflected a relative increase in the maximal secretory rate rather than increased burst half-duration. The estimated half-life (minutes) of endogenous FSH in LF women (155 +/- 18) was shorter than those calculated in EF (251 +/- 24), ML (277 +/- 38), and PM (231 +/- 18) women. Cross-correlation analysis showed strongly positive associations between successively paired serum FSH and LH concentrations in all four groups of women. Deconvolution of simultaneously obtained LH concentration-time series revealed statistically significant concordance (13-25%) between FSH and LH secretory episodes at a lag time of 0 min in EF, LF, and PM women and when LH secretory bursts led FSH secretory bursts by 10 min in ML phase women. However, as 75-87% of FSH and LH secretory pulses were discordant, we infer the operation of distinct control mechanisms in the generation of FSH and LH release episodes. In summary, these results suggest that FSH is secreted within discrete secretory bursts in women, that the mass and frequency of FSH secretory bursts differ in women exhibiting various gonadal hormone environments, and that FSH and LH secretory bursts occur coincidentally at a higher rate than expected on the basis of chance alone, but at such a low overall rate of concordance that distinct mechanisms probably operate to direct episodic FSH and LH secretory activity.
Assuntos
Estradiol/sangue , Hormônio Foliculoestimulante/metabolismo , Periodicidade , Pós-Menopausa/fisiologia , Progesterona/sangue , Adulto , Idoso , Feminino , Hormônio Foliculoestimulante/sangue , Fase Folicular/fisiologia , Meia-Vida , Humanos , Fase Luteal/fisiologia , Hormônio Luteinizante/sangue , Hormônio Luteinizante/metabolismo , Pessoa de Meia-IdadeRESUMO
Disordered reproductive function has long been recognized as a prevalent problem among women of reproductive age who suffer from insulin-dependent diabetes mellitus (IDDM). Delay in menarchial age is frequently seen if IDDM develops in the peripubertal years and some form of menstrual dysfunction is found in nearly one-third of all women of reproductive age with IDDM. This review summarizes some of the prevailing views regarding the mechanisms through which uncontrolled IDDM is thought to disrupt normal hypothalamic-pituitary-gonadal function. Although animal studies have suggested that poorly controlled IDDM may adversely affect the uterovaginal outflow tract and/or ovarian function, no clinical studies have suggested that abnormal uterine or ovarian function underlies the menstrual dysfunction observed in young diabetic women. Similarly, pituitary function as assessed by basal gonadotrophins and gonadotrophin-releasing hormone (GnRH)-stimulated gonadotrophin release appears to be normal in young women with IDDM. Moreover, although there has been some suggestion that pituitary function may decline with increasing duration of diabetes, this issue has not been thoroughly investigated. It appears that the oligo/amenorrhea noted in IDDM is principally hypothalamic in origin and may represent intermittent (and perhaps reversible) failure of the GnRH pulse generator, similar to the situation observed in women who engage in endurance training or who suffer from anorexia nervosa. Although the exact pathophysiological mechanisms that subserve dysfunction of the GnRH neuronal system are not well understood, attention has focused on increased central opioidergic activity, increased central dopaminergic activity, and central glucose deprivation. In this era of emphasis on tight glycaemic control and its impact in preventing diabetes complications, the consequences of IDDM on reproductive potential appear to be important and must be included in future investigative efforts.
Assuntos
Diabetes Mellitus Tipo 1/complicações , Distúrbios Menstruais/complicações , Animais , Diabetes Mellitus Tipo 1/fisiopatologia , Feminino , Humanos , Infertilidade Feminina/etiologia , Distúrbios Menstruais/epidemiologia , Distúrbios Menstruais/fisiopatologia , Reprodução/fisiologiaRESUMO
To investigate hypothalamic and/or pituitary abnormalities in women with poorly controlled insulin-dependent diabetes mellitus (IDDM) and secondary amenorrhea, we measured serum LH every 10 min for 24 h and for 2 additional h after the administration of exogenous GnRH in 8 women with IDDM and amenorrhea and compared these to data from 15 eumenorrheic nondiabetic women. LH pulses were characterized by the pulse detection algorithm Cluster, and secretory episodes were evaluated using the multiple parameter deconvolution procedure Deconv. Cluster analysis revealed fewer LH pulses per 24 h (14.3 +/- 1.2 vs. 19.9 +/- 0.6; P < 0.001; mean +/- SEM), a greater peak width (63 +/- 4.9 vs. 44 +/- 2.2 min; P < 0.01), and greater peak area (136 +/- 17 vs. 89 +/- 13 IU/L.min; P < 0.01) in the diabetic women. Analysis with Deconv revealed fewer LH secretory episodes per 24 h in the diabetic women (14.4 +/- 0.9 vs. 20.4 +/- 0.5; P < 0.001) and no statistical difference in LH half-lives. The IDDM women responded to a 10-micrograms GnRH bolus with LH pulses of larger total (51 +/- 15.9 vs. 15 +/- 1.4 IU/L; P < 0.01) and incremental (29 +/- 7.6 vs. 9 +/- 1.2; P < 0.001) amplitude. In summary, we observed that amenorrheic diabetic women have fewer LH pulses/secretory episodes than normal women. However, they respond well to exogenous GnRH, suggesting that compromise of the GnRH pulse generator, rather than pituitary dysfunction, is responsible for their menstrual dysfunction.
Assuntos
Amenorreia/etiologia , Amenorreia/metabolismo , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/metabolismo , Hormônio Luteinizante/metabolismo , Adulto , Algoritmos , Feminino , Hormônio Liberador de Gonadotropina , Meia-Vida , Humanos , Concentração Osmolar , Fluxo Pulsátil , Valores de ReferênciaRESUMO
OBJECTIVE: We sought to characterize pulsatile growth hormone (GH) release in normal women during the menstrual cycle and to document possible relationships between such characteristics and concentrations of 17 beta-oestradiol and progesterone. SUBJECTS: Fifteen women with ostensibly normal menstrual function were studied during the early follicular phase, 15 during the late follicular phase and 15 during the mid-luteal phase of the menstrual cycle. DESIGN: The phase of the menstrual cycle having been documented, blood samples were obtained from each woman every 10 minutes for 24 hours. MEASUREMENTS: Serum GH was measured in each sample by immunoradiometric assay. Pulsatile GH release was appraised utilizing the objective, statistically-based pulse detection algorithm Cluster. RESULTS: The mean (+/- SEM) integrated serum GH concentration (mU/l min) in late follicular phase women (5335 +/- 848) was higher than that observed in early follicular phase women (3156 +/- 322; P = 0.032). The integrated GH concentration calculated for mid-luteal phase women (3853 +/- 788) was intermediate between but not statistically different from that observed in early follicular (P = 0.48) and late follicular (P = 0.14) phase women. No differences in GH pulse frequency (pulses/24 hours) were found among early follicular (8.27 +/- 0.55), late follicular (7.93 +/- 0.91) or mid-luteal (8.47 +/- 0.66) phase women. Mean maximal GH pulse amplitude (mU/l) was higher in late follicular phase (8.93 +/- 1.00) than early follicular phase (5.74 +/- 0.67; P = 0.008) and mid-luteal phase (5.76 +/- 0.74; P = 0.008) women. Similarly, incremental GH pulse amplitude (mU/l) was higher in late follicular phase (7.33 +/- 0.83) than early follicular phase (4.68 +/- 0.58; P = 0.005) and mid-luteal phase (4.36 +/- 0.39; P = 0.002) women. No differences in mean pulse widths or in the interpeak valley mean GH concentrations were found among the groups. Multiple regression of each pulse parameter against serum concentrations of testosterone, 17 beta-oestradiol and progesterone revealed a significant (P = 0.045) positive correlation between maximum GH pulse amplitude and oestradiol and a significant (P = 0.04) negative correlation between maximal GH pulse amplitude and progesterone (r = 0.41). CONCLUSION: These results suggest that late follicular phase concentrations of oestradiol may enhance circulating GH via an amplitude-modulated rather than a frequency-modulated effect on the endogenous GH pulse. Progesterone may blunt this oestrogen-associated effect, thus resulting in the observed mid-luteal phase concentrations of GH. Whether these gonadal hormones act primarily at the hypothalamus and/or anterior pituitary gland remains to be clarified, but the present observations indicate that pulsatile GH release throughout the normal menstrual cycle is significantly amplitude regulated.
Assuntos
Hormônio do Crescimento/metabolismo , Menstruação/sangue , Adulto , Estradiol/sangue , Feminino , Fase Folicular/fisiologia , Hormônio do Crescimento/sangue , Humanos , Fase Luteal/fisiologia , Progesterona/sangue , Taxa Secretória/fisiologia , Testosterona/sangueRESUMO
The ability of psyllium fiber to reduce postprandial serum glucose and insulin concentrations was studied in 18 non-insulin-dependent diabetic patients in a crossover design. Psyllium fiber or placebo was administered twice during each 15-h crossover phase, immediately before breakfast and dinner. No psyllium fiber or placebo was given at lunch, which allowed measurement of residual or second-meal effects. For meals eaten immediately after psyllium ingestion, maximum postprandial glucose elevation was reduced by 14% at breakfast and 20% at dinner relative to placebo. Postprandial serum insulin concentrations measured after breakfast were reduced by 12% relative to placebo. Second-meal effects after lunch showed a 31% reduction in postprandial glucose elevation relative to placebo. No significant differences in effects were noted between patients whose diabetes was controlled by diet alone and those whose diabetes was controlled by oral hypoglycemic drugs. Results indicate that psyllium as a meal supplement reduces proximate and second-meal postprandial glucose and insulin concentrations in non-insulin-dependent diabetics.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/dietoterapia , Fibras na Dieta/uso terapêutico , Insulina/sangue , Psyllium/uso terapêutico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
To investigate the effect of glyburide on insulin secretion by individual beta cells from normal rats, we employed a reverse hemolytic plaque assay. Pancreata were harvested from female Wistar-Furth rats, the pancreatic islets isolated, and the latter dispersed into single cells. These cells were mixed with protein A-coated ox erythrocytes, the mixture was placed in a Cunningham chamber in the presence of insulin antiserum, and the cells were exposed to the various test substances. Having developed hemolytic plaques around the insulin-secreting cells with complement, the percentage of plaque-forming cells was determined and the plaque areas (reflecting the amount of insulin secreted) were quantitated. For the purpose of validation, we demonstrated that (i) plaque-forming (but not nonplaque-forming) cells could be identified as insulin secreting by an independent immunofluorescent technique, (ii), plaques did not form if insulin antiserum was deleted from the preparation, (iii) plaques failed to develop if insulin antiserum was preabsorbed with insulin, and (iv) incubation with non-protein A-coated RBC or omission of complement resulted in no plaque formation. In addition, both the percentage of plaque-forming cells and the mean plaque are increased upon exposure to glucose (0.75-20 mM) in a concentration-dependent manner at 5- and 60-min incubation times. Moreover, somatostatin suppressed the percentage of plaque-forming cells and diminished the mean plaque area of cells which continued to secrete insulin in response to glucose. Exposure of cells to 100 nM glyburide in the presence of 5 mM or 20 mM glucose had no effect on the percentage of plaque-forming cells present at 5 min or 60 min. Similarly, glyburide did not alter mean plaque area at 5 or 60 min when cells were co-incubated with 5 mM glucose. However, mean plaque area was markedly enhanced at 5 and 60 min in response to glyburide and 20 mM glucose. These results demonstrate that glyburide (i) does appear to enhance insulin secretion by an effect directly on the pancreatic beta cell; (ii) does not act by recruiting previously noninsulin-secreting cells into a secretory pool; (iii) does not potentiate the effect of glucose, at fed concentrations, on insulin secretion by individual cells; but (iv) does augment insulin secretion by beta cells stimulated with supraphysiologic concentrations of glucose.
Assuntos
Glucose/farmacologia , Glibureto/farmacologia , Insulina/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Feminino , Técnica de Placa Hemolítica , Técnicas In Vitro , Secreção de Insulina , Ratos , Ratos Endogâmicos WF , Somatostatina/farmacologiaRESUMO
Pulsatile and circadian patterns of PRL release were studied in 11 insulin-dependent diabetic men by sampling blood every 10 min for 24 h and comparing the results to those obtained in 12 normal nondiabetic men. The diabetic men had a mean (+/- SE) 24-h serum PRL concentration of 5.5 +/- 0.42 micrograms/L, which was significantly lower than that in the nondiabetic men (9.3 +/- 0.86; P = 0.0008). Quantitative Cluster analysis of pulsatile PRL time series revealed a normal pulse frequency, but decreased maximal peak amplitude (6.6 +/- 0.5 vs. 11.8 +/- 1.1 micrograms/L; P = 0.0009), peak increment (2.6 +/- 0.24 vs. 4.0 +/- 0.3 micrograms/L; P = 0.009), peak area (126 +/- 15 vs. 192 +/- 19 micrograms/L.min; P = 0.03), and interpulse valley mean concentration (4.8 +/- 0.4 vs. 8.6 +/- 1.2 micrograms/L; P = 0.0007). PRL pulse incremental amplitude correlated significantly (r2 = 0.577; P = 0.007) and negatively with duration of disease. Fourier analysis disclosed a normal circadian rhythm of PRL release in diabetic men, with a mean circadian amplitude of 1.5 micrograms/L +/- 0.31, which peaked at 0201 h +/- 89 min (+/- SE). In summary, we have demonstrated significantly reduced mean 24-h serum PRL concentrations in men with poorly controlled insulin-dependent diabetes mellitus. The concomitant suppression of spontaneous PRL pulse amplitude, peak increment, and interpulse valley mean concentrations in the presence of normal pulse frequency is consistent with a reduced mass of PRL secreted per burst and/or accelerated metabolic clearance of PRL in men with type I diabetes mellitus.
Assuntos
Diabetes Mellitus Tipo 1/sangue , Prolactina/sangue , Adulto , Glicemia/análise , Coleta de Amostras Sanguíneas , Ritmo Circadiano , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Prolactina/metabolismoRESUMO
The mechanisms responsible for the elevated levels of circulating GH observed in diabetes mellitus (DM) remain incompletely defined. To assess the episodic fluctuations in serum GH as a reflection of hypothalamic-pituitary activity, we accumulated GH concentration-time series in a total of 48 adult men and women with and without insulin-dependent DM by obtaining serum samples at 10-min intervals over 24 h. Significant pulses of GH release were subsequently identified and characterized by an objective, statistically based pulse detection algorithm (Cluster) and fixed circadian (24-h) periodicities of secretory activity, resolved using Fourier expansion time-series analysis. Compared to those in age-matched controls, integrated 24-h concentrations of GH were 2- to 3.5-fold higher in diabetic men (P = 0.002) and women (P = 0.0005). Both men and women with DM had over 50% more GH pulses per 24 h than their non-DM counterparts. In addition, maximal GH pulse amplitude was markedly elevated in the men and women with DM (P = 0.0019 and 0.0189, respectively). That the increase in maximal pulse amplitude was accounted for by greater baseline levels was documented by a higher interpulse valley mean GH concentration in the diabetics compared to the controls (P = 0.0437 and 0.0056, men and women, respectively) and the absence of any difference in incremental pulse amplitude for either sex (P greater than 0.05). DM men had larger GH pulse areas (P = 0.039) than control men, apparently accounted for by greater pulse width (P = 0.0037). Pulse areas in DM and non-DM women were indistinguishable. Time-series analysis revealed that the 24-h (circadian) rhythms of serum GH concentrations exhibited significantly increased amplitudes in the diabetic group as a whole (compared to the controls, P = 0.011). However, the times of maximal GH concentrations (acrophases) were not significantly different. As a group, serum insulin-like growth factor-I was lower in DM vs. non-DM individuals (P = 0.0014), although when separated by sex this difference did not reach statistical significance in women (P = 0.317). The present data confirm the higher circulating levels of GH previously reported to occur in individuals with poorly controlled DM. The altered frequency of GH pulses together with enhanced interpulse GH concentrations and an amplified circadian GH rhythm are compatible with hypothalamic dysfunction associated with dysregulation of somatostatin and/or GHRH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Diabetes Mellitus Tipo 1/sangue , Hormônio do Crescimento/sangue , Adulto , Fatores Etários , Peso Corporal , Ritmo Circadiano , Feminino , Hormônio do Crescimento/metabolismo , Humanos , Hipotálamo/fisiologia , Fator de Crescimento Insulin-Like I/sangue , Masculino , Hipófise/fisiologia , Fatores SexuaisRESUMO
Insulin autoantibodies (IAA) are frequently found in newly diagnosed untreated insulin-dependent diabetics. We evaluated whether the insulin antibody response over the first year of treatment with insulin was different in individuals with IAA v those without IAA. One hundred five previously untreated type I diabetics were randomly assigned to treatment with either pure porcine or mixed bovine/porcine insulin. Twenty-one in each group had detectable IAA at diagnosis. Percent binding rose in all patients after commencing insulin therapy and was significantly greater in those with IAA at diagnosis irrespective of the type of insulin administered. The elevated binding in the IAA positive patients at all time points was equivalent to the binding that could be attributed to the insulin autoantibodies. Two different mechanisms could explain this greater insulin antibody binding during insulin therapy in the IAA positive patients. First, there may be summation of binding due to insulin autoantibodies and binding due to insulin antibodies formed in response to the exogenous insulin. Alternatively, the insulin antibodies formed in response to exogenous insulin could replace the IAA, with those individuals positive for IAA at diagnosis having a proportionately greater antibody response to injected insulin. Irrespective of the mechanism, patients with IAA at diagnosis develop higher insulin antibody measurements when subsequently treated with exogenous insulin.
Assuntos
Autoanticorpos/análise , Diabetes Mellitus Tipo 1/imunologia , Anticorpos Anti-Insulina/análise , Criança , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Humanos , Masculino , PrognósticoRESUMO
Use of pure porcine insulin versus partially purified insulin of bovine/porcine origin might be expected to have certain clinical benefits, e.g., a lower incidence of skin reactions, a lower insulin dosage, better diabetes regulation, and greater preservation of endogenous insulin secretion. To test this hypothesis, we randomly assigned 112 newly diagnosed, untreated, insulin-dependent diabetic children to therapy with either pure porcine or partially purified bovine/porcine insulin. They were followed for 1 yr, data being available on at least 90 subjects at each visit. More skin reactions were found in the group treated with the bovine/porcine insulin. This insulin was of higher antigenicity, and binding of radiolabeled insulin (mean +/- SE) by serum from bovine/porcine insulin treatment was 35.5 +/- 2.6 versus 16.8 +/- 1.4% (P less than .001) for pure porcine insulin treatment 12 mo after initiation of insulin therapy. However, throughout the 12 mo of observation the levels of glycosylated hemoglobin, insulin dosage, fasting plasma glucose, and C-peptide concentration were similar for the groups. Reported incidences of hypoglycemia and nocturia were also similar. Thus, insulin-antibody formation and skin reactions were minimized by the use of pure porcine versus partially purified bovine/porcine insulin, but no other clinical advantages were apparent.
Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Insulina/uso terapêutico , Animais , Anticorpos/metabolismo , Peptídeo C/sangue , Bovinos , Criança , Ensaios Clínicos como Assunto , Toxidermias/etiologia , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Insulina/efeitos adversos , Insulina/imunologia , Masculino , Estudos Prospectivos , Distribuição Aleatória , Testes Cutâneos , SuínosRESUMO
Neuroglucopenia (NGP), which is a serious potential hazard for all insulin-treated diabetics, stimulates many neural and hormonal responses including increased glucagon secretion and activation of beta-adrenergic receptors of the autonomic nervous system. To determine which of these responses is important in recovery from NGP, we induced NGP in baboons by the intravenous (IV) injection of 2-deoxy-D-glucose with and without beta-adrenergic blockade (propranolol) and somatostatin. Thirty minutes after the induction of NGP the animals recovered, and the mean (+/- SEM) rise in arterial plasma glucose was 6.6 +/- 0.9 mmol/L, in glycerol 0.106 +/- 0.22 mmol/L, and in beta-hydroxybutyrate 0.091 +/- 0.22 mmol/L. Animal recovery and glucose rise were uninfluenced by the infusion of propranolol (mean 30 minute plasma glucose rise of 6.2 +/- 0.8 mmol/L) and somatostatin (6.8 +/- 0.8 mmol/L). However, the combined infusion of somatostatin and propranolol prevented animal recovery and glucose rise (1.0 +/- 0.1 mmol/L). The glycerol and beta-hydroxybutyrate rises were blocked by the propranolol infusion alone. Thus, recovery from NGP and the associated rise in plasma glucose, glycerol, and beta-hydroxybutyrate are prevented by the combination of the suppression of the glucagon and beta-adrenergic response to NGP. Furthermore, if the results of our study are extrapolated to insulin-dependent diabetic patients, most of whom have an impaired glucagon response to insulin-induced hypoglycemia/neuroglucopenia, they would be critically dependent on beta-adrenergic mechanisms for recovery from NGP.
Assuntos
Glicemia/metabolismo , Encefalopatias Metabólicas/sangue , Glucagon/sangue , Hipoglicemia/sangue , Receptores Adrenérgicos beta/fisiologia , Ácido 3-Hidroxibutírico , Animais , Desoxiglucose/farmacologia , Epinefrina/sangue , Glicerol/sangue , Hidroxibutiratos/sangue , Insulina/sangue , Masculino , Papio , Propranolol/farmacologia , Somatostatina/farmacologiaRESUMO
There is heterogeneity within insulin-dependent diabetes mellitus (IDDM), and it has been suggested that the presence of the HLA-DR specificities DR3 and DR4 define two subsets of IDDM with clear differences in their immune response to therapeutic insulin. To test this hypothesis, we have prospectively studies the development of insulin binding antibody (IBA) in 54 subjects with newly diagnosed, classical childhood IDDM, determined seven binding constants of their IBA, and measured the presence or absence of pancreatic polypeptide-binding antibodies after 1 yr of therapy with insulin. There were no relationships between insulin and pancreatic polypeptide antibodies and the DR3 or DR4 specificities whether these specificities were tested for alone or in combination, comparing the presence and absence of DR3 and DR4 and comparing DR3 with DR4, except that of the 33% of all subjects who developed antibodies binding pancreatic polypeptide by 1 yr, none possessed the DR3 specificity alone (P = 0.018). Thus, the hypothesis that the HLA-DR3 and -DR4 specificities are major determinants of IBA formation and, therefore, define important subsets of childhood IDDM in terms of immune response to therapeutic insulin is not substantiated by this study.
Assuntos
Diabetes Mellitus Tipo 1/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Insulina/uso terapêutico , Adolescente , Formação de Anticorpos , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/genética , Feminino , Antígenos HLA-DR , Antígeno HLA-DR3 , Antígeno HLA-DR4 , Humanos , Anticorpos Anti-Insulina/imunologia , Masculino , Estudos ProspectivosRESUMO
To investigate the mechanism whereby changes in plasma glucose level alter human pancreatic A-cell activity in vivo, A-cell activity was determined during manipulation of plasma glucose and pancreatic B-cell activity by insulin and glucose infusions. A-cell activity (the acute immunoreactive glucagon response to intravenous arginine, 0-10 min) rose from 482 +/- 125 to 968 +/- 191 pg X ml-1 X 10 min-1 (mean +/- SEM) when the plasma C-peptide level (a measure of B-cell activity) was suppressed from 2164 +/- 365 to 872 +/- 162 pg/ml by an insulin infusion at euglycaemia (employing the glucose clamp technique) in six normal subjects. Raising plasma glucose to 6.7 mmol/l during the same insulin infusion returned mean C-peptide (2688 +/- 581 pg/ml) and the acute glucagon response to arginine (447 +/- 146 pg X ml-1 X 10 min-1) close to basal levels. Individual changes in the acute glucagon response to arginine followed the C-peptide changes. The mean change in the acute glucagon response to arginine per unit change in plasma glucose (-191 +/- 36) was similar to that seen when plasma glucose was raised to twice basal levels in six different subjects without an insulin infusion (-159 +/- 45). This suggests that, when plasma glucose is raised to about twice basal level in vivo, the major factor in suppressing A-cell activity is the concurrent change in B-cell activity rather than direct effects of glucose or circulating insulin on the A cell.
Assuntos
Glicemia/fisiologia , Glucagon/metabolismo , Ilhotas Pancreáticas/fisiologia , Adolescente , Adulto , Arginina , Glicemia/análise , Peptídeo C/sangue , Glucagon/sangue , Humanos , Insulina/sangue , Masculino , RadioimunoensaioRESUMO
A sensitive assay was used to measure the binding of iodine-125-labeled insulin in serum obtained from 112 newly diagnosed insulin-dependent diabetics before insulin treatment was initiated. Two groups of nondiabetics served as controls: children with a variety of diseases other than diabetes and nondiabetic siblings of insulin-dependent diabetics. Eighteen of the diabetics were found to have elevated binding and 36 were above the 95th percentile of control values. The insulin-binding protein is precipitated by antibody to human immunoglobulin G, has a displacement curve that is parallel and over the same concentration range as serum from long-standing insulin-dependent diabetics, and elutes from a Sephacryl S-300 column at the position of gamma globulin. These insulin antibodies are present in a large percentage of newly diagnosed, untreated diabetics and may be an immune marker of B-cell damage.
Assuntos
Autoanticorpos/análise , Diabetes Mellitus Tipo 1/imunologia , Insulina/imunologia , Adolescente , Adulto , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Humanos , Insulina/uso terapêuticoRESUMO
Atherosclerosis of cerebral vessels (Grunnet 1963) and hypoglycaemia (Bale 1973) are thought to be involved in the premature intellectual deterioration which occurs in some diabetics. Two diabetics are now reported who, in the course of their investigation for intellectual deterioration, were found to have communicating hydrocephalus.
Assuntos
Complicações do Diabetes , Hidrocefalia/complicações , Inteligência , Processos Mentais , Feminino , Humanos , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
The role which the autonomic nervous system (ANS) plays in controlling glucagon (IRG) secretion is controversial. Strong activation of the ANS was achieved in baboons with 500 mg/kg 2-deoxyglucose, producing a 20-fold rise in epinephrine and a 15-fold rise in IRG. Under such circumstances, the IRG response was attenuated by both alpha- and beta-adrenergic blockade, strongly suggesting that this part of the IRG rise post 2-deoxyglucose was mediated via adrenergic mechanisms. The baboon is similar to man, with the sympatho-adrenal axis having little influence on IRG secretion during mild activation of the ANS. However, during stronger ANS activation with 2-deoxyglucose, a clear effect of the sympatho-adrenal axis on IRG secretion was demonstrated. Whether experiments in primates demonstrate an effect of the ANS on IRG secretion may depend primarily on the strength of the neural response elicted.
Assuntos
Sistema Nervoso Autônomo/fisiologia , Desoxiaçúcares/farmacologia , Desoxiglucose/farmacologia , Glucagon/metabolismo , Animais , Atropina/farmacologia , Glicemia/metabolismo , Epinefrina/sangue , Glucagon/sangue , Insulina/sangue , Cinética , Masculino , Papio , Fentolamina/farmacologia , Propranolol/farmacologiaRESUMO
To investigate whether glucose has an effect on the pancreatic A cell independent of intraislet or paracrine B cell mediation, we have tested the ability of changes in plasma glucose (PG) level to influence the acute glucagon response (AGR) to 5 g of intravenous arginine in 8 C-peptide negative insulin dependent diabetics (IDD). Insulin was infused (1 mU/kg/min) for a 90 min basal period during which PG levels were maintained constant by the glucose clamp technique. Basal AGR was then determined. In 4 of the diabetics, the PG level was subsequently lowered to a new steady state and, in 2 diabetics, PG level was raised. In 2 additional IDDs, two manipulations in PG level were carried out (PG ranges 51-390 mg/dl). The same insulin infusion was continued throughout. The acute glucagon response to arginine was determined at each PG level. The ability of unit changes in PG to influence (modulate) the AGR (MdIRG) was calculated as the difference in AGRs divided by the PG difference. MdIRG was consistent between diabetics (means +/- SEM = 2.1 +/- 0.2) and was independent of both direction and magnitude of the PG change. Thus, in vivo, in man, glucose has an effect on the pancreatic A cell which is independent of intraislet B cell influences.
Assuntos
Glucagon/metabolismo , Glucose/fisiologia , Ilhotas Pancreáticas/fisiologia , Adulto , Glicemia/análise , Diabetes Mellitus/fisiopatologia , Humanos , Insulina/administração & dosagem , MasculinoRESUMO
The "shock lung" syndrome may occur in diabetic ketoacidosis in association with disseminated intravascular coagulation; occasionally it occurs alone after treatment of the ketoacidosis. Two patients developed pulmonary opacities with clinical features of acute respiratory distress such as are seen in the shock lung syndrome; in both, however, the findings suggested a different mechanism from that occurring in the syndrome. Hypoalbuminaemia was prominent, and it is postulated that a low plasma osmotic pressure caused by high volume crystalloid infusions may have precipitated the acute respiratory complications. Plasma osmotic pressure may be an important variable in patients given large volumes of crystalloid infusions; further studies are required to elucidate mechanisms of pulmonary oedema in such patients.
Assuntos
Cetoacidose Diabética/tratamento farmacológico , Síndrome do Desconforto Respiratório/etiologia , Adulto , Cetoacidose Diabética/sangue , Humanos , Infusões Parenterais , Insulina/uso terapêutico , Masculino , Pressão Osmótica , Edema Pulmonar/etiologia , Albumina Sérica/análiseAssuntos
Autoanticorpos/análise , Infecções por Coxsackievirus/imunologia , Diabetes Mellitus Tipo 1/imunologia , Ilhotas Pancreáticas/imunologia , Anticorpos Antivirais/análise , Criança , Pré-Escolar , Infecções por Coxsackievirus/complicações , Diabetes Mellitus Tipo 1/etiologia , Enterovirus Humano B/imunologia , Feminino , Humanos , Masculino , Fatores de TempoRESUMO
To ascertain whether the ability of glucose to influence the pancreatic islets response to a nonglucose stimulus is normal in type II diabetics, we have evaluated the modulating effect (Md) of the plasma glucose level (PG) on the acute insulin response (IRI) and glucagon response (IRG) to intravenous arginine in noninsulin-dependent diabetics (NIDDM) and nondiabetics (ND). MdIRI or MdIRG is the change in the hormonal response to arginine resulting from changes in plasma glucose level divided by the change in plasma glucose. Md has been determined over two ranges of PG: between normal fasting PG (level I) and mild hyperglycemia (approximately 160 mg/dl, level II) and between mild hyperglycemia and marked hyperglycemia (approximately 350 mg/dl, level III). Increases in PG augmented the IRI response in both groups, but the degree of augmentation was impaired in the NIDDM group. MDIRI for ND and NIDDM between levels I and II were 20 +/- 3 and 1.9 +/- 0.6, respectively, and between levels II and III were 23 +/- 5 and 2.3 +/- 0.5, respectively (P less than 0.01). MdIRI correlated with fasting PG in ND and NIDDM. Changes in PG resulted in equivalent changes in the IRG response to arginine in both groups. MdIRG for level I to II was -6.2 +/- 1.0 and -6.0 +/- 1.2, and for level II and III was -0.9 +/- 0.4 and -1.2 +/- 0.5 in ND and NIDDM, respectively. The impairment of MDIRI and its relationship to fasting PG in NIDDM support the hypothesis that fasting hyperglycemia may be, in part, a compensatory mechanism for maintaining beta-cell response to nonglucose stimuli, thereby maintaining basal insulin levels. MdIRG was normal in NIDDM when evaluated at comparable glucose levels in the ND and NIDDM groups.