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Biomedical subjects

I Jialal

Publications and source records attributed to I Jialal.

At least 145 records · Page 8Linked to original sources
PubMed1986

The spectrum of non-insulin-dependent diabetes in the young in a migrant Indian population.

The familial aggregation and degree of adiposity of 108 Indian patients with non-insulin-dependent diabetes in the young was studied. All patients had onset of diabetes under 30 yr and the female to male ratio was 5:1. Obesity as defined was present in 52 patients (48.2%). A positive family history of diabetes was present in 90 patients (83.3%). Two distinct subtypes emerged in the patients with a positive family history; the offspring of conjugal diabetic parents (29%) and maturity onset diabetes of the young (MODY) with 3-generation transmission (13%). In conclusion, the syndrome of NIDDY in Indians comprises at least 3 subtypes: offspring of conjugal diabetic parents, MODY and patients without a family history (sporadic type).

Adolescent↗
PubMed1986

Microvascular complications and non-insulin-dependent diabetes of the young in South African Indians.

103 Indians (74 females, 29 males) with NIDDM diagnosed before age 30 yr on the basis of the revised WHO diagnostic criteria were studied in order to assess the prevalence of microvascular complications. The mean duration of NIDDM in the subjects was 11 yr (range 2-38 yr). 24 patients (23%) eventually required insulin therapy for control after a mean interval of 11.8 yr (range 5-38 yr). Diabetic retinopathy was present in 37 patients (35.9%), of whom 6 had proliferative retinopathy. Nephropathy was found in 16 patients (15.5%). The mean GFR of these patients was 46.8 ml/min, compared to a mean of 97.1 ml/min in 12 of the patients without nephropathy who had a similar mean duration of disease. The mean duration of disease in patients with retinopathy and nephropathy was 14.9 yr and 14.8 yr respectively. In the patients who eventually required insulin therapy both retinopathy (75%) and nephropathy (41%) were more common but the mean duration of disease in these patients was longer (16 yr vs 9 yr). This study has underlined the heterogeneity of NIDDM in the young, as microvascular complications are by no means uncommon in South African Indians with the disease.

Adolescent↗
PubMed1986

Thyroidectomy for life threatening giant familial goitre.

Urgent thyroidectomy for giant multinodular goitre causing airway obstruction was necessary in the mater familias of a family with a high prevalence of non-endemic goitre. Post operative complications are briefly discussed. Family screening revealed a 100% incidence of nodular goitre in eight first generation descendants with hyperthyroidism in one. A euthyroid pattern was found in 6 of these, as well as in 5 of 19 second generation descendants tested. In two of the first generation descendants dyshormonogenesis was excluded as an aetiological factor by the perchlorate discharge test.

Aged↗
PubMed1985

Is there a place for the estimation of free tri-iodothyronine levels in the diagnosis of hypothyroidism?

In this study free thyroxine (fT4) and free tri-iodothyronine (fT3) levels were assayed in 87 patients with a clinical diagnosis of hypothyroidism who had elevated thyrotrophin (TSH) levels (greater than 5.5 mU/l). fT4 levels were decreased in 72 of these 87 patients. However, only 44 of the 72 patients with low fT4 levels and increased TSH levels had a decreased concentration of fT3. The remaining 28 patients had normal fT3 levels. It appears that fT3 levels have little, if any, place in screening for hypothyroidism.

Adolescent↗
PubMed1985

Processing and transport of insulin by vascular endothelial cells. Effects of sulfonylureas on insulin receptors.

Polypeptide hormones such as insulin must cross the vascular barrier to mediate their biologic actions. A substantial vascular barrier may be encountered in muscle and fat tissues, which are supplied by continuous capillaries lined with tightly joined endothelial cells. Endothelial cells have previously been shown to bind and release insulin with minimal degradation. Because 125I-labeled insulin transport was demonstrated to be receptor-mediated, factors regulating insulin-receptor binding may also affect the insulin transport rate across the vascular barrier. Since sulfonylureas may have a glucose-lowering action by altering insulin receptors, the effects of tolazamide and glyburide on vascular endothelial cell insulin receptors were evaluated. Exposure of aortic endothelial cells in culture to insulin at 37 degrees C resulted in a 75 percent loss of receptors. Five to seven days of tolazamide exposure led to a 35 percent time-dependent increase in insulin binding. More strikingly, tolazamide altered the dose-receptor to insulin-induced down-regulation. Cells down-regulated with insulin (10 ng/ml) showed a 100 percent increase in binding in the presence of tolazamide; a dose-dependent effect occurred at the 75 to 200 micrograms/ml dosage level. Scatchard analysis indicated that the increase in 125I-labeled insulin binding was due to an increase in receptor number. When insulin receptors were identified with 125I-labeled insulin, tolazamide-treated cells clearly showed an increase of a band at Mr = 145 K, the alpha subunit of the receptor. Tolazamide may thus help normalize glucose in diabetes by preventing receptor down-regulation in endothelial cells.

Blood Vessels↗
PubMed1985

Lipid and lipoprotein aberrations in Indian patients with non-insulin-dependent diabetes in the young.

The present study was undertaken to examine the lipid and lipoprotein status of 85 Indian patients with non-insulin-dependent diabetes in the young (NIDDY) and 85 matched Indian controls. There were no significant differences between patients and controls with regard to total serum cholesterol, low-density lipoprotein (LDL) cholesterol or apoprotein A-I (apo A-I) levels. However, serum triglyceride and apo-protein B (apo B) levels (females only) were significantly higher and serum high-density lipoprotein (HDL) cholesterol levels significantly lower in the NIDDY patients than in the controls. Serum triglyceride values correlated significantly with glycosylated haemoglobin levels (r = 0,23), HDL cholesterol (r = -0,37) and apo B levels (r = 0,42). The hypertriglyceridaemia and increased apo B levels appeared to emanate from the very-low-density lipoprotein class. Since HDL cholesterol levels were decreased and apo A-I levels were normal, these findings could be interpreted as reflecting an abnormal HDL composition. Obesity did not appear to have a significant influence on the lipid and lipoprotein abnormalities manifested by the patients in this study.

Adolescent↗
PubMed1985

A plausible explanation for the aketonuria of young Indian non-insulin-dependent diabetics.

In an attempt to explain the rarity of ketonuria in Indian diabetics, plasma glucose, insulin and free fatty acid (FFA) levels were measured in 35 non-obese patients with non-insulin-dependent diabetes in the young and 35 matched controls during a 100 g oral glucose tolerance test. Compared with the controls, the patients had a severe degree of hyperglycaemia, fasting hyperinsulinism, and an attenuated and delayed insulinaemic response. However, in addition to the fasting plasma FFA levels being similar in the two groups, the decrement in the FFA responses was equivalent. Thus, the hormone-sensitive lipase of the adipose tissue appeared to be sensitive to inhibition by insulin. Also, the fasting insulin:glucagon molar ratios were computed and found to be no different in the two groups. The normal fasting FFA levels, relative sensitivity to insulin of lipolysis in the adipocyte and normal insulin: glucagon molar ratios may help to explain in part the general rarity of ketosis-prone diabetes in the South African Indian population.

Adult↗
PubMed1985

Insulin secretion in healthy Indian volunteers.

The insulin response to a 100 g oral glucose load was studied in 20 non-obese, healthy Indian females and 20 matched Indian males. There were no differences between the mean glucose responses of the two groups. However, early-phase (0-60 minutes) insulin release was significantly greater in the females. While there were no significant differences between the two groups when the total areas under the insulin and glucose curves were computed, the female volunteers had a significantly higher mean insulinogenic index. It therefore appears that healthy Indian females have significantly greater early-phase insulin release than their matched male counterparts.

Adult↗
PubMed1985

Isolated adrenocorticotrophic hormone (ACTH) deficiency associated with acute adrenal crisis.

A 37 year old black female presented with congestive cardiac failure, 2 months postpartum. She developed spontaneous hypoglycaemia and symptoms of acute adrenal crisis (hypotension, nausea, abdominal pain and tachycardia with small thready pulse), which responded to i.v. dextrose, sodium chloride and hydrocortisone. Biochemical investigations revealed low serum cortisol and plasma adrenocorticotrophic hormone (ACTH) levels. The patient initially showed an impaired cortisol response to intramuscular aqueous tetracosactrin, but an exuberant response after priming with intramuscular tetracosactrin depot. These findings, together with the normal remaining pituitary function, led us to conclude that this patient had isolated ACTH deficiency associated with congestive cardiac failure and acute adrenal crisis.

Acute Disease↗
PubMed1985

Characterization of the receptors for insulin and the insulin-like growth factors on micro- and macrovascular tissues.

Insulin and insulin-like growth factors (IGFs) have been implicated in the pathogenesis of diabetic retinopathy and peripheral vascular complications. Previously, we have shown that retinal capillary endothelial cells responded to insulin and IGFs for metabolic and growth effects, whereas aortic endothelial cells were not responsive. In contrast, vascular supporting cells from both retinal capillaries (i.e. pericytes) and aorta (i.e. smooth muscle cells) responded equally to insulin, IGF-I, and IGF-II. The structure and ligand specificities of the receptor for these peptides were studied by covalently cross-linking 125I-labeled peptide hormones to their respective receptors using disuccinimidyl suberate, followed by polyacrylamide gel electrophoresis and autoradiography. The binding subunit of the insulin receptor, alpha-subunit, for all cell types was found to have a mol wt 145,000 under reduced conditions. Labeling of this band was inhibited by 10(-9) M insulin, antiinsulin receptor antibodies, and 10(-8) M IGF-I, but not by multiplication-stimulating activity (IGF-II). The beta-subunit of the insulin receptor in endothelial cells was identified by its ability to be autophosphorylated when stimulated by insulin and was found to have a mol wt of 99,000. Covalent cross-linking of IGF-I to its receptor revealed a mol wt of 145,000, similar to that of insulin receptor, except that IGF-I was 100-fold more potent than insulin in competing with [125I]IGF-I for binding. [125I]IGF-II in all cells was cross-linked to receptor with mol wt of 260,000 and 230,000 under reduced and nonreduced conditions, respectively. IGF-I competed weakly with [125I]IGF-II, whereas insulin was ineffective. [125I]IGF-II also bound to the band with alpha mol wt of 135,000, which was inhibited by insulin, IGF-I, and IGF-II. In summary, receptors for insulin, IGF-I, and IGF-II on cells from micro- and macrovessels are biochemically similar to those in other cells. Interestingly, the finding of large numbers of IGF-I and IGF-II receptors on endothelial cells suggests that these growth factors play a physiological role and are involved in vascular complications associated with diabetes.

Animals↗
PubMed1985

The biochemical profile in Indian patients with non-insulin-dependent diabetes in the young with retinopathy.

A comparative study of the biochemical profile in 15 Indian patients with non-insulin-dependent diabetes in the young with retinopathy, and 15 matched patients without vascular disease, was undertaken. There were no significant differences between the lipid, lipoprotein and apoprotein levels between the 2 groups. While the fasting plasma glucose and glycosylated haemoglobin levels were significantly higher in the patients with retinopathy, there were no differences between the groups with regard to their insulin areas, glucose areas and insulinogenic indices. The retinopaths also had significantly lower serum magnesium levels than the patients without detectable retinal vascular disease.

Adult↗
PubMed1984

Insulin response to oral glucose in young, non-obese Indian males with myocardial infarction.

Plasma glucose and insulin concentrations were estimated during an oral glucose tolerance test (OGTT) in a group of 25 young (less than 40 years), non-obese Indian males 6-12 months after an episode of acute myocardial infarction and in 25 age- and sex-matched controls. All the subjects in both groups had a normal response to the OGTT according to the 1980 World Health Organization criteria. Glucose values during the OGTT and the mean plasma insulin response were significantly higher in the patients who had had a myocardial infarction. However, there was no significant difference in the insulinogenic indices. These findings indicate that Indian patients with myocardial infarction have aberrations in carbohydrate metabolism which manifest as higher glucose values during an OGTT and that the stimulated hyperinsulinism is secondary to these raised glucose levels.

Adult↗
PubMed1984

Insulin receptor regulation and desensitization in rat hepatoma cells. The loss of the oligomeric forms of the receptor correlates with the change in receptor affinity.

We have previously reported that prolonged incubations of Fao cells, a cell line derived from the well-differentiated Reuber H35 rat hepatoma, with 10(-6) M insulin, induced a decrease in receptor number (down-regulation), an increase in receptor affinity for insulin, and a loss of insulin's biological effect (desensitization). In the present study, we have investigated the relationship between these changes in insulin binding and action and changes in the structure of the insulin receptor. Intact cells were surface labeled with Na125I and lactoperoxidase, and the 125I-labeled insulin receptor was immunoprecipitated using specific antibodies and analyzed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Autoradiography of gels done under reducing conditions demonstrated the alpha (Mr = 135,000) and the beta (Mr = 95,000) subunits of the receptor. In nonreduced gels, free insulin receptor subunits were observed as well as four higher molecular weight bands with Mr = 210,000, 270,000, 350,000, and 520,000. Two-dimensional gel electrophoresis revealed that these bands correspond to alpha-beta heterodimer, alpha 2 homodimer, and two alpha-beta oligomers of high molecular weights, respectively. Cross-linking of 125I-insulin to intact cells with disuccinimidyl suberate revealed bands of Mr = 125,000, 210,000, 250,000 and 320,000, indicating that most of the forms of the receptor could bind insulin. After incubation with 10(-6) M insulin for 24 h, Fao cells revealed a marked decrease of the four oligomeric forms of the receptor, with little change in the level of the free alpha and beta subunits. A similar decrease of the oligomeric forms of the insulin receptor and an increase in the free subunits was observed when normal Fao cells are treated with 7 mM dithiothreitol. In dithiothreitol-treated cells, 125I-insulin binding was increased and this increase was accounted for by a change in affinity. In contrast to Fao cells, down-regulation of the insulin receptor in IM-9 lymphocytes occurs without a change in receptor affinity. In these cells, surface labeling revealed a decrease in total receptors after down-regulation, but not change in the proportion of the oligomeric forms to the free subunits of the receptor. These data suggest the following in Fao hepatoma cells. In the native state, the insulin receptor consists of free alpha and beta subunits and several kinds of disulfide-linked oligomers of these subunits.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

The growth hormone responses to L-dopa and TRH in acromegaly.

The GH responses to TRH and L-dopa were investigated in 14 Indian and African patients with untreated acromegaly. A positive response to L-dopa (greater than 50% change from basal) was obtained in 6 of the 14 patients tested while a positive response to TRH (greater than 100% change from basal) was found in 5 of 12 patients tested. While 9 patients responded to at least one agent, only 2 had a positive response to both agents. Positive responders appeared to be hyper-prolactinemic and have evidence of abnormal glucose tolerance as compared to nonresponders.

Acromegaly↗
PubMed1984

The metabolic response and problems with nutritional support in acute tetanus.

Thirteen patients with severe tetanus were studied in the first and second week of illness in order to assess metabolic changes and nutritional requirements. Nine required muscular paralysis and subsequent assisted ventilation in order to control spasms. Symptoms and signs of sympathetic overactivity were especially common in the latter groups with a fourfold increase in urinary adrenaline and noradrenaline excretion. Other hormonal and metabolic abnormalities included hyperglycemia, mildly elevated insulin concentrations with no significant rise in cortisol, and glucagon. Evidence of excessive protein catabolism was obtained particularly during the second week of illness, mean urinary nitrogen excretion being 20.5 +/- 13.8 g/d. Maintenance of nutrient homeostasis proved impossible with conventional enteral-feeding techniques: high-density feeds exacerbated hyperglycemia and diarrhea; low-density feeds were unable to maintain nitrogen balance (-12.34 g/d in ventilated patients, second week). The results indicate that loss of lean body mass is inevitable in such patients unless the metabolic response can be suppressed or more aggressive forms of nutritional support (eg, total parenteral nutrition including sufficient insulin to maintain normoglycemia) are employed.

Acute Disease↗