RESUMO
INTRODUCTION: Heritability in type 2 diabetes mellitus (T2DM) is observed but not well understood. METHODS: In this study, family history and clinical/biochemical data from 789 Bahrainis (418 T2DM, 371 controls) was analyzed. Fasting blood glucose (FBG) and HbA1c were measured and angiotensin-converting enzyme (ACE) and methylene tetrahydrofolate reductase (MTHFR) polymorphisms (SNPs) were analyzed. RESULTS: Patients compared to controls have higher proportions of diabetic mothers (50.2% vs. 32.7%, p=0.005), fathers (35.2% vs. 12.1%, p<0.001) and siblings (56% vs. 15.3%, p<0.001). The proportions of diabetic mothers was higher than the proportions of diabetic fathers among the patients (50.2% vs. 35.2%, p<0.001) and the controls (32.7% vs. 12.1%, p<0.001). Patients born to diabetic mothers compared to the other patients were smaller in age at the time of enrollment in this study (p=0.005), and at onset of T2DM (p<0.001), and also had higher FBG (p=0.033). Interestingly, the prevalence of T1DM was highest amongst the siblings of the controls compared to patients (p=0.04). Finally, the heterozygote I/D genotype of the ACE gene was over expressed in patients born to diabetic mothers when compared to patients born to diabetic fathers, p=0.007. CONCLUSIONS: there was strong clustering of T2DM in families, with significant dominant maternal role in transmission of T2DM and associated severity markers. Patients (T2DM) born to diabetic mothers were genetically and phenotypically different from the other patients.
Assuntos
Diabetes Mellitus Tipo 2/genética , Padrões de Herança/genética , Peptidil Dipeptidase A/genética , Idoso , Barein , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The controversial issue of the effects of prednisolone and 17 beta-estradiol on replication of fetal rat pancreatic islets in culture was studied using 32P and [3H]thymidine as probes for studying DNA synthesis. DNA synthesis was not affected by the steroid hormones, as was evident from the rate of incorporation of 32P into total DNA. Decreased incorporation of [3H]thymidine into DNA found in islets treated with either of these steroids seemed to reflect an inhibitory effect of these hormones on thymidine kinase, leading to decreased phosphorylation of labeled thymidine. In addition, the hormones stimulated the activity of thymidylate synthetase, thus enhancing the endogenous synthesis of thymidine and thereby diluting the specific activity of the [3H]thymidine added to the cultured islets. Further support for a lack of inhibition of growth of islet cells treated with steroid hormones was provided by the observation that prednisolone increased uridine kinase activity and RNA biosynthesis, both of which may participate in the growth of cells preceding mitosis and (the latter) in protein hormone biosynthesis.
Assuntos
Replicação do DNA/efeitos dos fármacos , Ilhotas Pancreáticas/citologia , Esteroides/farmacologia , Animais , Transporte Biológico/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , DNA/biossíntese , Estradiol/farmacologia , Ilhotas Pancreáticas/metabolismo , Prednisolona/farmacologia , RNA/biossíntese , Ratos , Timidina/metabolismo , Timidina Quinase/metabolismo , Timidilato Sintase/metabolismo , Uridina/metabolismo , Uridina Quinase/metabolismoRESUMO
Glibenclamide significantly stimulated the incorporation of [3H]thymidine into DNA of fetal rat pancreatic islets at a physiological (5.5 mM) but not at a high (22 mM) glucose concentration. There was no significant stimulation of insulin release under these conditions. In contrast, the drug-stimulated insulin release from adult islets cultured at 5.5 mM glucose but had no effect on their DNA synthesis. The observations suggest that insulin secretion and DNA synthesis may be dissociated in rat pancreatic islets.
Assuntos
Glibureto/farmacologia , Ilhotas Pancreáticas/citologia , Animais , Divisão Celular/efeitos dos fármacos , Replicação do DNA/efeitos dos fármacos , Feminino , Glucose/farmacologia , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Ratos , Ratos Endogâmicos , Timidina/metabolismoRESUMO
The mechanism of the inhibitory effect of steroid hormones, progesterone and prednisolone on the incorporation of [3H]-thymidine into pancreatic islet cell DNA was investigated. Treatment with either hormone had no effect on the incorporation of 32P-orthophosphate into islet cell DNA. Both prednisolone (10 microM) and progesterone (3 microM) markedly stimulated the activity of the enzyme thymidylate synthetase of islet cells possibly leading to increased synthesis of endogenous thymidine which resulted in dilution of the [3H]-thymidine added to the islets in tissue culture. Prednisolone (10 microM) significantly increased both insulin biosynthesis and release, while at 5 microM it was effective in increasing only insulin release. In contrast, progesterone at the two concentrations employed did not affect insulin biosynthesis or release. The smaller doses of both hormones markedly stimulated the total protein biosynthesis.
Assuntos
Ilhotas Pancreáticas/crescimento & desenvolvimento , Prednisolona/farmacologia , Progesterona/farmacologia , Animais , Divisão Celular/efeitos dos fármacos , Replicação do DNA/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Insulina/biossíntese , Insulina/metabolismo , Secreção de Insulina , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/fisiologia , Masculino , Fosfatos/metabolismo , Ratos , Ratos Endogâmicos , Timidilato Sintase/metabolismoRESUMO
We have previously reported that infection with Plasmodium yoelii, Plasmodium chabaudi, or injection of extracts from malaria-parasitized red blood cells induces hypoglycemia in normal mice and normalizes the hyperglycemia in streptozotocin (STZ)-diabetic mice. P yoelii glycosylphosphatidylinositols (GPIs) were extracted in chloroform:methanol:water (CMW) (10:10:3), purified by high-performance thin layer chromatography (HPTLC) and tested for their insulin-mimetic activities. The effects of P yoelii GPIs on blood glucose were investigated in insulin-resistant C57BL/ks-db/db diabetic mice. A single intravenous injection of GPIs (9 and 30 nmol/mouse) induced a significant dose-related decrease in blood glucose (P < .001), but insignificantly increased plasma insulin concentrations. A single oral dose of 2.7 micromol GPIs per db/db mouse significantly lowered blood glucose (P < .01). P yoelii GPIs in vitro (0.062 to 1 micromol/L) significantly stimulated lipogenesis in rat adipocytes in a dose-dependent manner both in the presence and absence of 10(-8) mol/L insulin (P < .01). P yoelii GPIs stimulated pyruvate dehydrogenase phosphatase (PDH-Pase) and inhibited both cyclic adenosine monophosphate (cAMP)-dependent protein kinase A and glucose-6-phosphatase (G6Pase). P yoelii GPIs had no effect on the activity of the gluconeogenic enzymes fructose-1,6-bisphosphatase (FBPase) and phosphoenolpyruvate carboxykinase (PEPCK). This is the first report of the hypoglycemic effect of P yoelii GPIs in murine models of type 2 diabetes. In conclusion, P yoelii GPIs demonstrated acute antidiabetic effects in db/db mice and in vitro. We suggest that P yoelii GPIs, when fully characterized, may provide structural information for the synthesis of new drugs for the management of diabetes.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucose/metabolismo , Glicosilfosfatidilinositóis/farmacologia , Homeostase/efeitos dos fármacos , Hipoglicemiantes , Plasmodium yoelii/química , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Glicemia/metabolismo , Cromatografia em Camada Fina , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Relação Dose-Resposta a Droga , Frutose-Bifosfatase/metabolismo , Glucose-6-Fosfatase/metabolismo , Insulina/sangue , Lipídeos/biossíntese , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Obesos , OxirreduçãoRESUMO
Recurrent hereditary polyserositis (RHP), also known as familial Mediterranean fever, is a genetically-determined disease characterized by paroxysmal attacks of peritonitis, pleuritis, arthritis or inflammation of other serous membranes. We have previously suggested that the pathogenesis of this disease seems to be related to abnormal catecholamine metabolism. This study compares the plasma and urine catecholamine profile in patients with RHP during different clinical states to that in controls. In RHP there were lower plasma and higher urine dopamine levels in the asymptomatic state and during attacks, while norepinephrine levels remain unchanged. However, plasma epinephrine was significantly lower in the asymptomatic state but markedly higher during attacks. The urine epinephrine values in both situations were similar but significantly lower than in controls, suggesting abnormal renal excretion of epinephrine. The urine metanephrine was markedly elevated in the asymptomatic state compared to controls, but remained unchanged during the attacks, again suggesting defective renal clearance of metanephrine. Metaraminol infusion, which induces attacks in RHP patients, was associated with an increase in plasma dopamine and epinephrine (but not norepinephrine); yet the urinary levels of dopamine, epinephrine and metanephrine remained the same, confirming the dissociation between the plasma and urinary levels of these catecholamines, probably due to abnormalities in the renal clearance mechanism. We postulate that this dissociation leads to retention of these amines in the plasma which may subsequently leak through the serous membranes (the target organs) and incite an acute inflammatory process. Colchicine, the only known drug that protects against disease attacks, reduces the plasma levels of these amines, and thus may act by preventing retention that leads to leakage and subsequent inflammation.
Assuntos
Catecolaminas/metabolismo , Febre Familiar do Mediterrâneo/metabolismo , Catecolaminas/sangue , Catecolaminas/urina , Colchicina/farmacologia , Colchicina/uso terapêutico , Dopamina/metabolismo , Epinefrina/metabolismo , Febre Familiar do Mediterrâneo/tratamento farmacológico , Feminino , Humanos , Masculino , Metanefrina/urina , Metaraminol/farmacologia , Metaraminol/uso terapêutico , Norepinefrina/metabolismo , Normetanefrina/urina , Valores de Referência , Estresse Fisiológico/metabolismoRESUMO
Severe asthma and diabetes have been reported not to co-exist in the same patient. Various studies have attributed this to the possible association of asthma with hyperinsulinism, increased responsiveness to insulin or to beta-blockade. Previous studies have not addressed all these possible mechanisms in the same patient. In this prospective study, 7 atopic asthmatics and 7 age and sex-matched healthy controls underwent glucose, insulin and glucagon tolerance tests. The results showed no evidence of hyperinsulinism or increased responsiveness to insulin. Intravenous administration of glucagon, however, showed a lesser increase of glucose and insulin in asthmatics. Since glucagon has a beta-agonist effect on the liver and activates glycogenolysis and gluconeogenesis via beta-receptor stimulation and stimulates insulin secretion by activating adenylate cyclase of pancreatic beta-cells through beta-receptors, the results of glucagon tolerance test in our study may therefore suggest the presence of partial beta-blockade in atopic asthmatics.
Assuntos
Asma/metabolismo , Asma/fisiopatologia , Glicemia/metabolismo , Glucagon/farmacologia , Receptores Adrenérgicos beta/fisiologia , Adulto , Humanos , Injeções Intravenosas , Insulina/farmacologia , Masculino , Fatores de TempoRESUMO
The effect of lipoprotein-deficient serum (LPDS) with and without added low-density lipoprotein (LDL), isolated from diabetic subjects, on the replication of SV40-transformed islet cells (HIT cells) was investigated. Whole serum as well as LPDS preparations stimulated DNA synthesis maximally when added to the culture medium at a final concentration of 0.1%. The addition of LDL at 25 and 175 micrograms protein/ml medium did not cause further stimulation. On the contrary, the higher concentrations resulted in a significant inhibition. These results suggest that previously observed stimulation of DNA synthesis in smooth muscle cells by LDL from diabetic subjects is most likely due to the presence of growth factors in the serum of these patients and not to LDL per se.
Assuntos
DNA/biossíntese , Diabetes Mellitus Tipo 2/sangue , Ilhotas Pancreáticas/patologia , Lipoproteínas LDL/fisiologia , Fenômenos Fisiológicos Sanguíneos , Divisão Celular/fisiologia , Linhagem Celular Transformada , Humanos , Insulina/metabolismo , Secreção de Insulina , Ilhotas Pancreáticas/metabolismoRESUMO
The reported prevalence of type 2 diabetes among the Kuwaiti population varied from one source to another. This study was undertaken to define the magnitude of the problem and to suggest plans for future diabetic care. All type 2 Kuwaiti diabetic subjects registered and continuing to attend regularly in two health areas Mubarak Health Area (MHA) and Farwania Health Area (FHA)] were selected for the study. There were 3222 in MHA and 5114 in FHA among the Kuwaiti population aged 20 years and above, accounting for a total crude prevalence of 7.6% in both health areas and for a prevalence rate of 5.6% in MHA and 10.0% in FHA. The age-specific prevalence of type 2 diabetes in both areas combined rose from 2.639 per 100 population in the age group 20-39 years to 15.350% and 26.252% in the age groups 40-59 and 60 and above, respectively. The female to male ratio was 1.7, 1.6, 1.1, respectively, in MHA and 1.7, 2.0, 0.9 in FHA for the age groups 20-39, 40-59, and 60 and above. This study shows that type 2 diabetes is a major public health problem in Kuwait, with a female preponderance. Obesity is a characteristic feature of the population studied, with a mean body mass index of 31.8 +/- 6.3 and 28.5 +/- 5.1 in women and men, respectively. A positive family history of diabetes mellitus was reported in 63% of the diabetic subjects. There is a need to standardize methods of reporting and to plan a national screening survey.
Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Kuweit , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores SexuaisAssuntos
Carcinoma Hepatocelular/enzimologia , Fígado/enzimologia , Neoplasias Experimentais/enzimologia , Pentosefosfatos/metabolismo , Animais , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/metabolismo , Etionina , Glucoquinase/metabolismo , Gluconatos/metabolismo , Glucosefosfato Desidrogenase/metabolismo , Hexoquinase/metabolismo , Hexosefosfatos/metabolismo , Fígado/metabolismo , Neoplasias Hepáticas , Neoplasias Experimentais/metabolismo , Fosfoglucomutase/metabolismoAssuntos
Fígado/metabolismo , Nucleotídeos de Adenina/metabolismo , Ciclo do Ácido Cítrico , Coenzima A/metabolismo , Citoplasma/metabolismo , Gluconeogênese , Fígado/citologia , Malatos/metabolismo , Matemática , Mitocôndrias/metabolismo , Modelos Biológicos , NAD/metabolismo , NADP/metabolismo , Oxaloacetatos/metabolismo , Oxirredução , Pentosefosfatos/metabolismo , Fosfatos/metabolismo , Fosfofrutoquinase-1/metabolismoAssuntos
Glucoquinase/metabolismo , Hexoquinase/metabolismo , Tecido Adiposo/enzimologia , Animais , Encéfalo/enzimologia , Feminino , Frutose , Glucoquinase/sangue , Glucose , Hexoquinase/sangue , Humanos , Isoenzimas/metabolismo , Cinética , Lactação , Leucócitos/enzimologia , Fígado/enzimologia , Pulmão/enzimologia , Masculino , Glândulas Mamárias Animais/enzimologia , Matemática , Gravidez , Ratos , Espectrofotometria Ultravioleta , Fatores de Tempo , DesmameAssuntos
Coenzima A/análise , Glândulas Mamárias Animais/análise , Oxo-Ácido-Liases , Acetatos/metabolismo , Acetilcoenzima A/análise , Animais , Dióxido de Carbono/biossíntese , Isótopos de Carbono , Citrato (si)-Sintase , Citosol/análise , Feminino , Glucose/metabolismo , Lactação , Glândulas Mamárias Animais/citologia , Glândulas Mamárias Animais/enzimologia , Glândulas Mamárias Animais/metabolismo , Matemática , Mitocôndrias/análise , Gravidez , Piruvatos/metabolismo , OvinosAssuntos
3',5'-AMP Cíclico Fosfodiesterases/metabolismo , Fígado/enzimologia , Diester Fosfórico Hidrolases/metabolismo , Tireoidectomia , Adenilil Ciclases/metabolismo , Animais , Peso Corporal , Membrana Celular/enzimologia , GMP Cíclico , Técnicas In Vitro , Cinética , Masculino , Tamanho do Órgão , RatosAssuntos
Venenos de Serpentes/farmacologia , Peçonhas/farmacologia , Animais , Glicemia , Pressão Sanguínea/efeitos dos fármacos , Permeabilidade Capilar/efeitos dos fármacos , Gatos , Feminino , Cobaias , Coração/efeitos dos fármacos , Técnicas In Vitro , Masculino , Músculo Liso/efeitos dos fármacos , Potássio/sangue , Coelhos , Sódio/sangueAssuntos
Escorpiões , Peçonhas/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Gatos , Cromatografia em Papel , Eletroforese , Feminino , Cobaias , Coração/efeitos dos fármacos , Técnicas In Vitro , Intestino Delgado/efeitos dos fármacos , Dose Letal Mediana , Camundongos , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Junção Neuromuscular/efeitos dos fármacos , Coelhos , Ratos , Respiração/efeitos dos fármacos , Especificidade da Espécie , Estimulação Química , Útero/efeitos dos fármacos , Peçonhas/análise , Peçonhas/toxicidadeAssuntos
Eletrólitos/metabolismo , Venenos de Escorpião/farmacologia , 17-Cetosteroides/urina , Fosfatase Alcalina/sangue , Animais , Cálcio/metabolismo , Eletrólitos/sangue , Eletrólitos/urina , Absorção Intestinal , Masculino , Fósforo/metabolismo , Potássio/metabolismo , Ratos , Sódio/metabolismoAssuntos
Colelitíase/metabolismo , Bile/análise , Cálcio/análise , Colesterol/análise , Humanos , Fósforo/análise , SudãoRESUMO
OBJECTIVE: The mechanisms underlying insulin resistance during normal pregnancy, and its further exacerbation in pregnancies complicated by gestational diabetes mellitus (GDM), are generally unknown. Inositolphosphoglycan P-type (P-IPG), a putative second messenger of insulin, correlates with the degree of insulin resistance in diabetic subjects. An increase during normal pregnancy, in maternal and fetal compartments, has recently been reported. METHODS: A cross-sectional study was carried out in 48 women with GDM and 23 healthy pregnant women. Urinary levels of P-IPG were assessed spectrophotometrically by the activation of pyruvate dehydrogenase phosphatase in urinary specimens and correlated with clinical parameters. RESULTS: Urinary excretion of P-IPG was higher in GDM than in control women (312.1 +/- 151.0 vs. 210.6 +/- 82.7 nmol NADH/min/mg creatinine, P < 0.01) with values increasing throughout pregnancy in control subjects (r2 = 0.34, P < 0.01). P-IPG correlated with blood glucose levels (r(2) = 0.39, P < 0.01 for postprandial glycaemia and r2 = 0.18 P < 0.01 for mean glycaemia) and birthweight in the diabetic group (r2 = 0.14, P < 0.01). CONCLUSIONS: Increased P-IPG urinary excretion occurs in GDM and positively correlates with blood glucose levels. P-IPG may play a role in maternal glycaemic control and, possibly, fetal growth in GDM.