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Biomedical subjects

M Viswanathan

Publications and source records attributed to M Viswanathan.

At least 19 recordsLinked to original sources

The islet amyloid polypeptide gene and non-insulin-dependent diabetes mellitus in south Indians.

Islet amyloid polypeptide (IAPP), otherwise called amylin, is the monomeric component of islet amyloid. Deposition of this amyloid is a characteristic feature of non-insulin-dependent diabetes mellitus in humans and may play a role in the pathogenesis of the disease. As such, abnormalities in the structure or expression of the IAPP gene might contribute to the inheritance of this condition. The IAPP gene was studied in a well-characterised population of 62 unrelated Dravidian subjects with non-insulin-dependent diabetes mellitus and 56 normal Dravidian controls, using a restriction fragment length polymorphism generated by PvuII digestion. Genotype and allele frequencies did not differ between diabetic subjects and controls. Taken together with recent findings in Europid and other racial groups, an abnormality of the IAPP gene is highly unlikely to represent a major gene for the development of non-insulin-dependent diabetes mellitus.

Alleles

Prevalence of childhood diabetes in an urban population in south India.

The objective of the study was to estimate the prevalence of insulin-dependent diabetes in children less than or equal to 15 years in an urban area in south India, by a population study. Three zones from the northeastern part of the city demarcated by the Directorate of Census were chosen. Ascertainment of the cases from these zones was made (a) by collecting data from the major hospitals and diabetes clinics by personal visit; (b) by questionnaire sent to medical practitioners in the area; and (c) from the chemists and druggists who sell insulin. Recommendations of the Diabetes Epidemiology Research International Registry Group were used. Thirty children with insulin-dependent diabetes with age at diagnosis less than or equal to 15 years were identified. The prevalence was 0.26/1000. The peak age at diagnosis was 12 years. This first population-based study of prevalence of insulin-dependent diabetes in south India shows that insulin-dependent diabetes is not rare. It is higher than reported from many other Asian countries.

Adolescent

Comparative study of the clinical profiles of alcoholic chronic pancreatitis and tropical chronic pancreatitis in Tamil Nadu, south India.

In a comparative study of tropical chronic pancreatitis (TCP) and alcoholic chronic pancreatitis (ACP) occurring in the same population, we analyzed the clinical profile of 50 patients of ACP seen over the past 3 years at our centers and compared this with the profile of our TCP patients. A majority (75%) of patients in both groups belonged to Tamil Nadu and 90% had never consumed cassava. Whereas TCP occurred in young subjects of both sexes, ACP patients were all males and presented at an older age. The frequency of pain, diabetes, and pancreatic calcification was similar in the two groups. Patients in both groups were lean, but signs of severe malnutrition were rare. Prediabetic patients had normal body mass index. There were striking differences in radiological appearance of pancreatic calculi in TCP and ACP. Malignancy of the pancreas was present in three patients with TCP. Benign bile duct stenosis was seen in three patients with ACP but not in TCP. Compared to ACP seen in the West, our ACP patients had a shorter duration of symptoms in spite of having advanced disease. TCP and ACP have distinct clinical profiles and it is possible that some environmental factors may hasten the progress of ACP in the tropics.

Abdominal Pain

Clinical and biochemical studies in the prediabetic phase of tropical calcific pancreatitis.

The frequency of diabetes is much higher in tropical calcific pancreatitis (TCP) as compared with alcoholic chronic pancreatitis. We report 97 patients with tropical calcific pancreatitis and compare the profile of 21 patients without diabetes (called TCP for the purpose of this report) with that of 76 patients with diabetes, called fibrocalculous pancreatic diabetes (FCPD) according to the World Health Organization (WHO) study group classification of diabetes. TCP patients were a decade younger and had marginally higher body mass indices (BMIs) as compared with the FCPD group. Of the TCP patients, 13 had abnormal glucose tolerance tests (GTT) and the others had normal GTT. Immunoreactive insulin (IRI) responses to glucose load in the TCP group did not differ significantly from that of the control group. This study shows the existence of early stages of glucose intolerance in TCP.

Adolescent

Differential expression of melatonin receptors in spontaneously hypertensive rats.

Quantitative autoradiography was used to compare melatonin receptors in brain areas and arteries of young (4 weeks old) and adult (14 weeks old) spontaneously hypertensive rats (SHR) to those in age-matched normotensive controls, Wistar-Kyoto (WKY) rats. Age and strain influenced the number of melatonin receptors in an anatomically selective manner, and the most striking changes occurred in arterial receptors. Melatonin receptors were not detectable in the anterior cerebral arteries of adult SHR. In the caudal artery, melatonin receptors decreased with age in both strains, but the decrease was more pronounced in SHR. When compared to age-matched WKY rats, the number of caudal artery receptors was higher in young and lower in adult SHR. The number of melatonin receptors was higher in the area postrema of adult SHR when compared to adult WKY rats, but in the suprachiasmatic nucleus, no such differences between the two strains were present. Alterations in receptor density were not accompanied by changes in binding affinity. Our results indicate that in the rat melatonin receptors show different developmental patterns according to location and that the receptors may be expressed differentially in genetic hypertension.

Age Factors

Balloon angioplasty enhances the expression of angiotensin II AT1 receptors in neointima of rat aorta.

Angiotensin II is a vasoactive peptide and may act as a growth factor in vascular smooth muscle cells. Experimental injury of the rat aorta causes rapid migration of medial smooth muscle cells and their proliferation resulting in the formation of neointima. We have examined, using quantitative autoradiography, the expression of angiotensin II receptor subtypes AT1 and AT2, and angiotensin-converting enzyme, in the neointima formed in the rat thoracic aorta 15 d after balloon-catheter injury. In contrast to the normal aortic wall, which contained both AT1 and AT2 receptors (80% and 20%, respectively), neointimal cells expressed almost exclusively angiotensin II AT1 receptors. The apparent number of these receptors was fourfold higher in the neointima compared to that in the normal aortic wall. The affinities of the neointimal receptors to angiotensin II or to the AT1 receptor antagonist, losartan, were not different from those in the normal aortic wall. Angiotensin-converting enzyme binding in the neointima was not different from that in the media of the uninjured aorta. Our data suggest that angiotensin II AT1 receptors may have a significant role in injury-induced vascular smooth muscle proliferation and migration.

Angioplasty, Balloon

Differential regulation of the rat melatonin receptors: selective age-associated decline and lack of melatonin-induced changes.

To gain some understanding of the factors regulating high affinity melatonin (MT) receptors in the rat, we conducted a series of studies using quantitative autoradiography of [2-125I]iodo-MT binding in vitro with validated assay conditions. MT receptor status and the relative protein content of the autoradiographic sections were assessed in the anterior pituitary gland, the area postrema, the caudal (tail) artery (CA), the anterior cerebral artery (ACA), and the suprachiasmatic nuclei (SCN) of 9-, 96-, and 306-day-old Wistar rats. When age-associated changes in protein content were taken into account, MT receptor expression in the area postrema and the SCN remained relatively constant between 9-306 days of age. On the contrary, a dramatic loss of MT receptors was observed in the arteries of 306-day-old rats (98% and 89% loss compared to the 9-day-old rats in the ACA and CA, respectively). In the anterior pituitary gland, MT receptors were expressed only in the 9-day-old rats. The above changes reflected major changes in binding capacity and minor changes in binding affinity. Neither removal of endogenous circulating MT (acute light exposure for 24 h, pinealectomy, or superior cervical ganglionectomy) nor MT injections (1 mg/kg for 10 days 6 h after lights on) affected MT receptor status in the ACA, CA, area postrema, or SCN. Our data suggest that MT receptor expression is differentially regulated during development and that permanent alterations in MT levels do not affect rat MT receptor status.

Age Factors

Melatonin-binding sites in brain and caudal arteries of the female rat during the estrous cycle and after estrogen administration.

Melatonin-binding sites were studied by quantitative autoradiography in brain and caudal (tail) arteries and in selected brain areas of cycling female rats, ovariectomized rats, and ovariectomized rats treated with estradiol. In the caudal artery, the number of melatonin-binding sites was significantly lower during proestrus, estrus, and metestrus than during diestrus. In ovariectomized rats, melatonin binding to the caudal artery was similar to that found during proestrus, estrus, and metestrus, and a further decrease in the receptor number was produced by estradiol replacement. Similarly, melatonin binding in anterior cerebral arteries was higher during diestrus than at other stages of the estrous cycle. In ovariectomized rats, estradiol replacement also resulted in decreased melatonin binding in anterior cerebral arteries. Conversely, no changes in the number of melatonin-binding sites were observed in the suprachiasmatic nucleus or the area postrema during the estrous cycle, in ovariectomized rats, or after estradiol replacement. The present results suggest that in the female rat, reproductive hormones modulate the expression of cerebral and caudal arterial melatonin-binding sites.

Animals

Prevalence of glucose intolerance in Asian Indians. Urban-rural difference and significance of upper body adiposity.

OBJECTIVE: To evaluate the prevalence of NIDDM and IGT in the urban and rural areas in southern India. RESEARCH DESIGN AND METHODS: Two populations of the same ethnic background, but different socioeconomic background were chosen for this study. Nine-hundred urban people and 1038 rural subjects were studied. Fasting and 2-h post-glucose capillary blood samples after a 75 g oral glucose load (WHO criteria) were obtained in these randomly selected adults (greater than or equal to 20 yr of age). RESULTS: Using the WHO criteria, the prevalence of NIDDM, adjusted to the age of the respective general population, was 8.2% in the urban and 2.4% in the rural populations. The prevalence was 8.4 and 7.9%, respectively, in urban men and women, and 2.6 and 1.6% in rural men and women. The age-adjusted prevalence of IGT was 8.7 and 7.8% in the urban and rural areas, respectively. The prevalence of IGT was 8.8% in urban men and 8.3% in women; the corresponding values for rural men and women were 8.7 and 6.4%. The prevalence of NIDDM increased with age, markedly so in the urban people. The urban-rural difference was significant for NIDDM (chi 2 = 29.4, P less than 0.001) but not for IGT. In the urban population, 65% of the NIDDM patients were known cases, whereas in the rural area, the known cases accounted for only 24%. Bivariate analysis showed an association of BMI, STR, and WHR with prevalence of NIDDM plus IGT. In the multiple logistic regression analysis, age, BMI, STR, and WHR were associated significantly with glucose intolerance in the urban population, whereas only age was significant in the rural population. The best predictors of NIDDM were age, BMI, WHR, and urbanization. CONCLUSIONS: The study showed a high prevalence of NIDDM in the urban southern Indian population. The prevalence of NIDDM in the same ethnic group in rural areas was significantly lower. The prevalence of IGT was similar in both populations. Upper body adiposity was a significant predictor of NIDDM in this population with low rates of obesity.

Adipose Tissue

The genetics of non-insulin-dependent diabetes mellitus in south India: an overview.

Non-insulin-dependent diabetes mellitus affects approximately 10% of urban Indian and Indian migrant populations and as such carries major health implications for these groups. Whilst a strong genetic component to the aetiology of non-insulin-dependent diabetes mellitus is incontestable, progress in identifying the specific genetic determinants involved in its pathogenesis has been slow. In studies of South Indian pedigrees, preliminary segregation analysis indicates that non-insulin-dependent diabetes mellitus is likely to be a polygenic disease. A number of candidate genes have been studied with the aim of demonstrating either association or linkage with the disease; in South Indians the only positive results thus far have been associations between non-insulin-dependent diabetes mellitus and the genes for insulin, apolipoprotein D and complement component C4B. However, it seems likely that these genes contribute only a small proportion of the genetic susceptibility to non-insulin-dependent diabetes mellitus in this ethnic group and that the major genes underlying glucose intolerance remain to be determined.

Apolipoproteins

Glucagon response to glucose load in offspring of conjugal type 2 diabetic parents in south India.

Immunoreactive glucagon responses were measured in 21 normoglycaemic adult offspring of non-insulin dependent (Type 2) diabetic parents, in the fasting state and during an oral glucose tolerance test. In 7 of the 21 offspring, the mean fasting immunoreactive glucagon value was significantly lower than the control value (p < 0.001). In this group, glucose stimulation did not produce inhibition of immunoreactive glucagon secretion. The insulin response in this group was not significantly different from the values in the other study groups. In the other 14 offspring, the pattern of glucagon response to glucose stimulation was similar to controls. It is likely that this non-suppressive effect of glucose on immunoreactive glucagon in some of the "prediabetic" individuals is an early change in the alpha cell function during the natural history of non-insulin dependent diabetes in Asian Indian subjects.

Adult

Insulin responses to varying hyperglycaemia in newly diagnosed non-insulin dependent diabetic patients.

The effect of varying degrees of hyperglycaemia on insulin secretion was studied in newly diagnosed non-insulin dependent diabetic patients, stratified according to the fasting plasma glucose values. Of the 116 patients studied, 62 were non-obese and 54 obese. Insulin response patterns during 2h oral glucose tolerance test were analysed in comparison with the values in weight matched control subjects and also with respect to the degree of hyperglycaemia. The effect of hyperglycaemia on beta cell secretion differed in obese and non-obese patients. In the non-obese, fasting insulin levels were within normal range even in those with severe hyperglycaemia while the corresponding values in response to glucose stimulation showed a decreasing pattern. In obese patients, even fasting immunoreactive insulin (IRI) value was decreased and with increasing hyperglycaemia the reduction in IRI response to glucose stimulation was of greater magnitude compared to non-obese patients. Thus the modulating effect of obesity on insulin secretion appears to disappear with development of hyperglycaemia. The insulinogenic index was low in all the diabetic patients.

Adult

Angiotensin II AT1 receptors in rat superior cervical ganglia: characterization and stimulation of phosphoinositide hydrolysis.

Angiotensin II receptor number was higher in superior cervical ganglia of 2-week-old when compared to 8-week-old rats. In both young and adult rats, specific binding of [125I][Sar1]angiotensin II was displaced competitively by the AT1-receptor antagonist DuP 753 but not by the AT2-receptor competitor PD 123177. In ganglia from adult rats, DuP 753 competed with an IC50 of 113 nM. The stable guanine nucleotide GTP gamma S inhibited binding of [125I][Sar1]angiotensin II in young and adult rats by approximately 50% with IC50 values of 105 and 120 nM, respectively, suggesting that the angiotensin receptor is G-protein linked. Angiotensin II at a dose of 1 microM stimulated inositol phosphate formation 58% over control values in superior cervical ganglia from 8-week-old rats. This effect was totally blocked by 10 microM DuP 753 but not by 10 microM PD 123177. Our findings demonstrate that rat superior cervical ganglia contain AT1-type angiotensin receptors that are probably G-protein linked, and their stimulation results in increased inositol phospholipid metabolism.

Angiotensin II

Changes in expression of angiotensin receptor subtypes in the rat aorta during development.

Quantitative autoradiography was used to characterize angiotensin AT1 and AT2 receptors, in the rat aorta at three developmental ages; embryonic day 18 (E18), and postnatal weeks 2 and 8. The expression of angiotensin receptors was higher in the aorta of E18 and 2-week-old rat. A major proportion of the angiotensin receptors expressed in the aorta at these two ages was AT2 (84 and 81% respectively). Conversely, in the aorta of 8-week-old rats, AT1 was the predominant angiotensin receptor subtype (71%). In 8-week-old rats, the AT2 subtype was also present (28%). In pre- and postnatal rats, [125I]Sar1-angiotensin II binding to AT1 receptors was sensitive to GTP gamma S whereas binding to AT2 receptors was not. AT2 receptors may serve an important role during stages of rapid growth of the aorta, and also have a significant function in the adult vasculature.

Aging

Type-1 and type-2 angiotensin II receptors in fetal rat brain.

Brain angiotensin II receptors were located in 18-day-old rat embryos by quantitative autoradiography. In the nucleus of the solitary tract and choroid plexus, binding was displaced by the type-1 antagonist DuP 753. In the inferior olive, paratrigeminal and hypoglossal nuclei, binding was displaced by the type-2 antagonist CGP 42112 A. Meninges and cephalic soft tissues contained predominantly type-2 angiotensin II receptors. Our results indicate a role for type-1 and type-2 angiotensin II receptors during brain development.

Angiotensin II

Nutritional profile of fibrocalculous pancreatic diabetes and primary forms of diabetes seen in southern India.

Plasma levels of retinol binding protein (RBP), prealbumin, total protein, albumin, transferrin and ferritin were estimated in three groups of diabetic patients seen at a diabetes centre in S. India. The groups consisted of patients with fibrocalculous pancreatic diabetes (FCPD), non-insulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM). Mean RBP levels were lower in FCPD and IDDM patients compared to controls but this did not reach statistical significance. Prealbumin levels were normal in FCPD patients, but low in IDDM compared to controls (P less than 0.005) and NIDDM (P less than 0.05). FCPD patients had lower transferrin levels compared to controls (P less than 0.05). There were no differences in the levels of total protein, albumin and ferritin in any of the study groups. The study shows that biochemical evidence of undernutrition is seen in FCPD and IDDM patients while NIDDM patients are not significantly different from non-diabetic control subjects.

Adult

Increased calcium influx in caudal artery of rats made hypertensive with pyridoxine deficiency.

Moderate pyridoxine deficiency in rats has been shown to induce hypertension, which can be corrected by pyridoxine supplementation. In this study, calcium handling by isolated caudal arteries from pyridoxine-deficient and age-matched control rats was evaluated. We found 45Ca influx into the intracellular compartment to be significantly elevated in deficient rats. This increased influx could be attenuated with nifedipine, a calcium channel blocker, in a dose-dependent manner, suggesting alterations in the calcium channels that would make them leaky. The pyridoxine-deficient arterial segments maintained a higher resting tone; removal of extracellular calcium by EGTA or entry blockade by nifedipine decreased the tone significantly in the deficient arteries, compared with little or no effect in controls.

Animals