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Biomedical subjects

L Ranganath

Publications and source records attributed to L Ranganath.

12 recordsLinked to original sources
PubMed1999

Inhibition of carbohydrate-mediated glucagon-like peptide-1 (7-36)amide secretion by circulating non-esterified fatty acids.

Two studies were performed to assess the entero-insular axis in simple obesity and the possible effect of variations in the level of circulating non-esterified fatty acids (NEFA) on one of the components of the entero-insular axis, glucagon-like peptide-1 [(7-36) amide]. In the first study, we compared the entero-pancreatic hormone response to oral carbohydrate in obese and lean women. Obese subjects demonstrated hyperinsulinaemia and impaired glucose tolerance but this was not associated with an increased secretion of either glucose-dependent insulinotropic polypeptide or glucagon-like peptide-1 (GLP-1). These findings therefore provide no support for the hypothesis that overactivity of the entero-insular axis contributes to the hyperinsulinaemia seen in obesity. Indeed, the plasma GLP-1 response to carbohydrate was markedly attenuated in obese subjects, confirming previous observations. In the second study, in which carbohydrate-stimulated GLP-1 responses were again evaluated in obese and lean women, circulating NEFA levels were modulated using either heparin (to increase serum NEFA) or acipimox (to reduce serum NEFA). Treatment with acipimox resulted in complete suppression of NEFA levels and in a markedly higher GLP-1 response than the response to carbohydrate alone or to carbohydrate plus heparin. We suggest that higher fasting and postprandial NEFA levels in obesity may tonically inhibit nutrient-mediated GLP-1 secretion, and that this results in attenuation of the GLP-1 response to carbohydrate. However, although serum NEFA levels post-acipimox were similarly suppressed in both lean and obese subjects, the GLP-1 response was again significantly lower in obese subjects, suggesting the possibility of an intrinsic defect of GLP-1 secretion in obesity. The reduction of GLP-1 levels in obesity may be important both in relation to its insulinotropic effect and to its postulated role as a satiety factor.

Adult↗
PubMed1999

The effect of circulating non-esterified fatty acids on the entero-insular axis.

BACKGROUND: Circulating non-esterified fatty acids (NEFAs) have been causally associated with impairment of glucose metabolism, although their effect on the entero-insular axis, either in obesity or health, is unknown. MATERIALS AND METHODS: Glucose, insulin, glucagon-like peptide-1 (7-36 amide) (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) responses to 100 g of carbohydrate in 400 mL water were evaluated during simultaneous modulation of circulating non-esterified fatty acids (NEFAs). A total of 10,000 units of heparin (to increase serum NEFAs) and 500 mg of acipimox (2 h before oral carbohydrate ingestion to reduce serum NEFAs) were administered to seven obese [mean +/- SEM: age 40 +/- 3.7 years; body mass index (BMI) 38.9 +/- 2.1 kg m-2] and seven lean (age 39.6 +/- 3.6 years; BMI 22.4 +/- 0.4 kg m-2) women. RESULTS: Higher fasting levels and post-heparin total integrated NEFAs (P < 0.05) and glycerol (P < 0.05) responses were seen in the obese than in the lean group. Incremental integrated GLP-1 responses to oral carbohydrate post-heparin in lean (P < 0.01) and obese (P < 0.05) subjects were significantly lower than after acipimox. Total integrated GIP (P < 0.05) and glucose (P < 0.01) responses were higher post heparin than after acipimox in obese subjects only. CONCLUSION: The inverse relationship in GIP and GLP-1 responses in the obese group after modulation of NEFAs indicates that reciprocal changes between these two hormones may exist to ensure constancy of B-cell stimulation. Our results suggest that in obese subjects compensatory secretion of GIP was incomplete and could not prevent impairment in glucose tolerance after heparin-induced rise in NEFAs. These results may be important in understanding the role of the insulinotropic hormones in carbohydrate metabolism characterized by high NEFA levels such as obesity and diabetes mellitus.

Adult↗
PubMed1998

Delayed gastric emptying occurs following acarbose administration and is a further mechanism for its anti-hyperglycaemic effect.

The therapeutic effect of acarbose is generally attributed to inhibition of amylase and brush border glucosidases and consequent impaired digestion and absorption of carbohydrates. We have investigated the possibility that acarbose may also influence the rate of gastric emptying by comparing plasma glucose and gastrointestinal hormone responses to an oral sucrose load with and without acarbose in 11 healthy subjects. Gastric emptying was assessed indirectly by measuring circulating paracetamol concentrations following administration of paracetamol along with the sucrose load. Peak plasma glucose, insulin, and glucose-dependent insulinotropic polypeptide (GIP) responses were reduced when sucrose was given with acarbose. There was a significant reduction in post-sucrose paracetamol levels with acarbose suggestive of a significant delay in gastric emptying. The failure of acarbose to induce change in circulating paracetamol concentrations until after 60 min is indicative of a delay in gastric emptying rather than an osmotic malabsorption. The exaggerated and sustained release of glucagon-like peptide-1 (7-36)amide (GLP-1) seen when sucrose was given with acarbose may play a part in the inhibition of gastric emptying. This study indicates that a significant delay in gastric emptying may be an added mechanism contributing to the therapeutic effect of acarbose.

Acarbose↗
PubMed1998

The ageing entero-insular axis.

Ageing is one of the major risk factors for glucose intolerance including impaired glucose tolerance and Type II (non-insulin-dependent) diabetes mellitus. Reduced insulin secretion has been described as part of normal ageing although there is no information on age-related changes in the secretion of the major insulinotropic hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide (7-36 amide) (GLP-1). We assessed the entero-insular axis in 6 young premenopausal and 6 older postmenopausal women following treatment with oral carbohydrate. Insulin and glucose integrated responses were similar in the younger and older groups. Total integrated responses for GIP and GLP-1 were considerably greater in the older subjects. A positive correlation between age and total integrated responses for glucose (r = 0.65; p < 0.02) as well as GLP-1 (r = 0.85; p < 0.001) was seen. We hypothesise that an age-related impairment of insulin secretion to insulinotropic hormones, GIP and GLP-1, contributes to a reduction in glucose tolerance in this age group. The pronounced compensatory increase in postprandial secretion of GIP and GLP-1 provides further evidence not only for the negative feedback relation between incretin and insulin secretion but also for the importance of the entero-insular axis in the regulation of insulin secretion.

Acetaminophen↗
PubMed1998

Value of assessing parathyroid hormone-like activity in a case of extreme hypercalcaemia.

A previously well 70 year old woman was admitted to hospital following a three day history of vomiting and confusion. Her serum calcium was 6.58 mmol/l, phosphate 1.09 mmol/l, and alkaline phosphatase 91 iu/l. The mechanism of this hypercalcaemia was not obvious as there was no evidence of a primary malignancy, lymphadenopathy or hepatosplenomegaly. The calculation of indices of urinary excretion of calcium and phosphate suggested the presence of excessive parathyroid hormone (PTH) activity as the mechanism of hypercalcaemia. Plasma intact PTH, 25-hydroxycholecalciferol, and 1,25-dihydroxycholecalciferol were not raised suggesting the presence of PTH related peptide (rP). This led to a systematic search for a malignancy, which revealed the presence of a high grade B cell non-Hodgkin's lymphoma confined to the bone marrow. Plasma PTH-rP was subsequently shown to be raised confirming the interpretation of the initial urinary and calcium excretion indices. This case highlights the value of standard laboratory measurements such as urinary calcium and phosphate excretion in cases of hypercalcaemia of obscure aetiology, which can complement measurements of PTH and other calcitropic hormones.

Aged↗
PubMed1996

A seven-day Helicobacter pylori treatment regimen using clarithromycin, omeprazole and tripotassium dicitrato bismuthate.

AIM: To evaluate clarithromycin 500 mg t.d.s., tripotassium dicitrato bismuthate 240 mg b.d. and omeprazole 20 mg b.d. for 7 days as a Helicobacter pylori treatment regimen. METHODS: The H. pylori status of dyspeptic patients undergoing endoscopy was assessed by histology, culture and rapid urease testing of biopsies and by 13C-urea breath test. Fifty patients who were H. pylori-positive were treated with the above treatment regimen for 7 days. Those patients with active duodenal ulcers present at endoscopy were given omeprazole 20 mg nocte for a further 21 days. Not less than 28 days after completing treatment, all tests were repeated to reassess H. pylori status. Bacterial sensitivity of H. pylori cultures was determined and patients recorded any side-effects. RESULTS: On an intention-to-treat basis, H. pylori infection was cured in 90% (95% CI: 78-96%) of patients. Taste disturbance was experienced by 35% patients. Compliance was excellent, with 96% patients taking more than 95% of tablets. Metronidazole resistance was 41% but all cultures were sensitive to clarithromycin. CONCLUSIONS: This 7-day treatment achieved a high level of cure of H. pylori infection with relatively minor side-effects. It may have a role to play, particularly where there is a high level of metronidazole resistance.

Adult↗
PubMed1989

Bone disease in chronic alcoholism: the value of plasma osteocalcin measurement.

Osteoporosis is more common in chronic alcoholics than in age-matched controls. Possible aetiological factors are: malabsorption of calcium and vitamin D; liver disease and abnormal parathyroid function. The possibility that alcohol may directly affect osteoblastic function has, however, received little attention. We measured plasma osteocalcin, a protein synthesised specifically by osteoblasts, in chronic alcoholics. Our data show that these have low plasma osteocalcin but normal calcium, magnesium and parathormone, which suggest that alcohol may be directly toxic to osteoblasts.

Adult↗
PubMed1989

Impaired renal tubular function in chronic alcoholics.

Despite the well known effects of chronic alcohol abuse on the gastrointestinal, cardiovascular, nervous and endocrine systems, little information is available on its effect on renal function. To assess renal function we measured urinary excretion of albumin, alpha 1 microglobulin and retinol binding protein in 30 chronic alcoholic patients. Our data shows that 40% of chronic alcoholic patients have impaired renal tubular function.

Adult↗
PubMedDate not supplied

Visual function during acute hypoglycaemia.

Hypoglycaemia symptoms are of particular interest in view of the importance of hypoglycaemia unawareness. Visual symptoms arising during acute hypoglycaemia may be the result of metabolic disturbances in the visual pathways within the central nervous system or impairment of the refractive apparatus of the eye and binocular function. This study investigated the effect of hypoglycaemia upon visual acuity, binocular interaction and contrast sensitivity. Various aspects of visual function were examined in ten normal subjects before, during and after acute insulin-induced hypoglycaemia. A simultaneous study of hypoglycaemic symptoms enabled us to relate the objective findings to the symptoms as reported by the subjects. Snellen visual acuity, fusion and stereopsis were not affected by hypoglycaemia. Five subjects noted visual disturbance. Eight developed significant impairment of contrast sensitivity, which closely matched the lowered blood glucose concentration. These observations suggest that hypoglycaemic visual symptoms are due to neuroglycopenia of central visual pathways rather than changes within the refractive apparatus or abnormality of binocular function. Although these symptoms are not a constant feature of the hypoglycaemic state, subtle impairment of visual function occurs in most cases. Contrast sensitivity testing can be useful for assessment of fine changes in visual function.

Accommodation, Ocular↗