Glucagon-like peptide 1 (GLP-1) is potentially a very attractive agent for treating type 2 diabetes. We explored the effect of short-term (1 week) treatment with a GLP-1 derivative, liraglutide (NN2211), on 24-h dynamics in glycemia and circulating free fatty acids, islet cell hormone profiles, and gastric emptying during meals using acetaminophen. Furthermore, fasting endogenous glucose release and gluconeogenesis (3-3 Hglucose infusion and 2 H 2 O ingestion, respectively) were determined, and aspects of pancreatic islet cell function were elucidated on the subsequent day using homeostasis model assessment and first-and second-phase insulin response during a hyperglycemic clamp (plasma glucose ϳ16 mmol/l), and, finally, on top of hyperglycemia, an arginine stimulation test was performed. For accomplishing this, 13 patients with type 2 diabetes were examined in a double-blind, placebo-controlled crossover design. Liraglutide (6 g/kg) was administered subcutaneously once daily. Liraglutide significantly reduced the 24-h area under the curve for glucose (P ‫؍‬ 0.01) and glucagon (P ‫؍‬ 0.04), whereas the area under the curve for circulating free fatty acids was unaltered. Twenty-four-hour insulin secretion rates as assessed by deconvolution of serum C-peptide concentrations were unchanged, indicating a relative increase. Gastric emptying was not influenced at the dose of liraglutide used. Fasting endogenous glucose release was decreased (P ‫؍‬ 0.04) as a result of a reduced glycogenolysis (P ‫؍‬ 0.01), whereas gluconeogenesis was unaltered. First-phase insulin response and the insulin response to an arginine stimulation test with the presence of hyperglycemia were markedly increased (P < 0.001), whereas the proinsulin/insulin ratio fell (P ‫؍‬ 0.001). The disposition index (peak insulin concentration after intravenous bolus of glucose multiplied by insulin sensitivity as assessed by homeostasis model assessment) almost doubled during liraglutide treatment (P < 0.01). Both during hyperglycemia per se and after arginine exposure, the glucagon responses were reduced during liraglutide administration (P < 0.01 and P ‫؍‬ 0.01). Thus, 1 week's treatment with a single daily dose of the GLP-1 derivative liraglutide, operating through several different mechanisms including an ameliorated pancreatic islet cell function in individuals with type 2 diabetes, improves glycemic control throughout 24 h of daily living, i.e., prandial and nocturnal periods. This study further emphasizes GLP-1 and its derivatives as a promising novel concept for treatment of type 2 diabetes.

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Hepatic fructose-6-phosphate (fructose-6-P) cycling and pentose cycle activity were quantified in hyperthyroid patients. A measure of the fructose-6-P cycle was the incorporation of 14C, on administering [3-3H,6-14C]galactose, into carbon 1 of blood glucose and the 3H/14C ratio in blood glucose. The measure of the pentose cycle was the randomization of 14C to carbon 1 of blood glucose on administering [2-14C]galactose. [2-3H]Galactose was also administered, so the 3H/14C ratio in blood glucose measured the extent of equilibration of glucose-6-P with fructose-6-P. Patients given [3-3H,6-14C]galactose were restudied when euthyroid. Of the 14C from [3-3H,6-14C]galactose, 7.7-9.5% was in carbon 1 of glucose in both states. 3H/14C ratios were also the same in both states. Fructose-6-P cycling was estimated to be 13 +/- 1% the rate of glucose turnover in the euthyroid and 15 +/- 1% that in the hyperthyroid state. The pentose cycle contributed about 2% to glucose utilization, similar to previous estimates in healthy humans. As in healthy individuals, about 25% of 3H was retained in the conversion of [2-3H]glucose-6-P to glucose. Thus, the fractions of glucose turnover participating in hepatic fructose-6-P and pentose cycling are similar in hyperthyroid and healthy subjects. As a result, augmented fructose-6-P cycling does not substantially contribute to increased hepatic oxygen consumption in hyperthyroidism.

Guwahati, the lone city on the bank of the entire midstream of the Brahmaputra River, is facing acute civic problem due to severe depletion of water quality of its natural water bodies. This work is an attempt towards water quality assessment of a relatively small tributary of the Brahmaputra called the Bharalu River flowing through the city that has been transformed today into a city drainage channel. By analyzing the key physical, chemical and biological parameters for samples drawn from different locations, an assessment of the dissolved load and pollution levels at different segments in the river was made. Locations where the contaminants exceeded the permissible limits during different seasons were identified by examining spatial and temporal variations. A GIS developed for the watershed with four layers of data was used for evaluating the influence of catchment land use characteristics. BOD, DO and total phosphorus were found to be the sensitive parameters that adversely affected the water quality of Bharalu. Relationship among different parameters revealed that the causes and sources of water quality degradation in the study area were due to catchments input, anthropogenic activities and poor waste management. Elevated levels of total phosphorus, BOD and depleted DO level in the downstream were used to develop an ANN model by taking total phosphorus and BOD as inputs and dissolved oxygen as output, which indicated that an ANN based predictive tool can be utilized for monitoring water quality in the future.

Pancreatic islets from healthy (control) and neonatally streptozocin-induced diabetic (STZ-D) rats, a model for non-insulin-dependent diabetes mellitus, were incubated with 3H2O and 5.5 or 16.7 mM glucose. At 5.5 mM glucose, no detectable [3H]glucose was formed. At 16.7 mM, 2.2 patom.islet-1.h-1 of 3H was incorporated into glucose by the control islets and 5.4 patom.islet-1.h-1 by STZ-D islets. About 75% of the 3H was bound to carbon-2 of the glucose. Glucose utilization was 35.3 pmol.islet-1.h-1 by the control and 19.0 pmol.islet-1.h-1 by the STZ-D islets. Therefore, 4.5% of the glucose-6-phosphate formed by the control islets and 15.7% by the STZ-D islets was dephosphorylated. This presumably occurred in the beta-cells of the islets catalyzed by glucose-6-phosphatase. An increased glucose cycling, i.e., glucose----glucose-6-phosphate----glucose, in islets of STZ-D rats may contribute to the decreased insulin secretion found in these animals.

Antisera prepared by immunization of rabbits with human T4-binding globulin (TBG) contained two populations of antibodies: one directed against determinants of the native molecule, and the other directed against antigenic sites present only in denatured TBG. These two populations of antibodies were present in all nine antisera prepared in this or other laboratories that were tested. Exploiting this property of anti-TBG sera and using radioiodinated denatured TBG as a tracer, a RIA was developed which measures specifically denatured TBG in the presence of native TBG. The RIA for measuring denatured TBG used purified native TBG, which was denatured by reduction and pyridylethylation (RP-TBG) before labeling with 125I. Native TBG was measured using the same antiserum, but the 125I-labeled tracer was unmodified TBG. The sensitivity of the native TBG RIA was 0.25 ng purified native TBG. Equivalent amounts of native TBG in serum, desialylated TBG, and deglycosylated TBG produced superimposeable standard curves. The cross-reactivity with RP-TBG was less than 0.02%. The denatured TBG RIA had a sensitivity of 1 ng, and superimposeable curves were produced with equivalent concentrations of RP-TBG and heat-denatured native TBG. The cross-reactivity of 0.8% with native and deglycosylated TBG was, at least in part, due to denatured TBG in the purified preparations. The specificity of the two RIAs is due to the existence of distinct and exclusive antigenic determinants in native TBG and denatured TBG which are probably located on the surface of the tertiary structure and internally at the primary structure of the molecule, respectively. Heat and acid pH treatments of serum produced a progressive loss in immunoreactive native TBG, proportional to the loss of T4-binding capacity. A reciprocal and quantitative increase in denatured TBG, as measured in the denatured TBG RIA, was found. T4 partially protected the native TBG from denaturation. Denatured TBG was detected in sera from normal adults. The mean value was 6.05 +/- 2.25 (+/- SD) micrograms/dl (n = 11). Similar values were found in 8 pregnant women, 5 men with familial partial TBG deficiency, and 15 hypothyroid 7 hepatic, and 8 renal failure patients.(ABSTRACT TRUNCATED AT 400 WORDS)