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Query: UMLS:C0011849 (diabetes)
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Responses of plasma immunoreactive gastric inhibitory polypeptide (IRGIP) to oral triglyceride or galactose were compared in normal and mildly diabetic (non-insulin-dependent) subjects. After triglyceride the responses of IRGIP were similar, but after galactose those of the diabetics were slightly exaggerated. Both stimuli evoked increments of plasma immunoreactive glucagon (IRG) in diabetics but not in normal subjects. Plasma immunoreactive insulin (IRI) did not change. In normal subjects given oral triglyceride or galactose followed by intravenous (I.V.) glucose the early-phase response of plasma IRI was enhanced and glucose tolerance improved. In the diabetics, oral triglyceride did not affect insulin release or glucose tolerance after I.V. glucose; oral galactose elicited a slight increase of insulin release without improving glucose tolerance. In the diabetics the rise of plasma IRG after ingestion of triglyceride or galactose was maintained after I.V. glucose. It is concluded that endogenous GIP is insulinotropic and that there is partial resistance to this action in diabetes. The results were compatible with feedback inhibition of GIP secretion by insulin and with the suggestion that the rise of plasma IRG associated with secretion of GIP in diabetics may be due to the glucagonotropic action of this peptide.
Diabetes 1978 Mar
PMID:Effects of ingestion of triglyceride or galactose on secretion of gastric inhibitory polypeptide and on responses to intravenous glucose in normal and diabetic subjects. 64 Feb 38

The alpha and beta anomers of commercially available D-(5-3H) glucose were separated by miniaturized Hudson-Dale procedures based on precipitation with acetic acid. Reflectometric measurements of the reactivity with matrix-bound glucose oxidase showed that the preparations were about 90 per cent pure with respect to anomeric composition. Nonradioactive anomers separated by the same procedures were analyzed by optic polarimetry and gas chromatography. The preparations were about 90 per cent pure with respect to anomeric composition and produced no peaks but D-glucose on trimethylsilylation and chromatography. Microdissected pancreatic islets of noninbred ob/ob-mice exhibited a linear production of 3H2O for three to nine minutes when incubated with 6 mM alpha-D-(5-3H) glucose, beta-D-(5-3H) glucose, or D-(5-3H) glucose in anomeric equilibrium; the three glucose preparations did not differ in their rate of conversion to 3H2O. The rate of 3H2O production increased with glucose concentration (3-21 mM) during incubations for three minutes and, again, there was no evidence for the metabolic activity's being dependent on the anomeric composition of the labeled sugar. When microdissected islets were perifused without glucose and suddenly exposed to 5-6 mM alpha-D-glucose or beta-D-glucose, the concentration of glucose-6-phosphate rose within five minutes and did not differ significantly between experiments with alpha-D-glucose and beta-D-glucose. In the same perifusion experiments, only alpha-D-glucose caused a pronounced stimulation of insulin secretion, the difference from beta-D-glucose being significant. The results indicate that the recognition of glucose as an insulin secretagogue does not only involve metabolism by glucose-6-phosphate. The possible roles of the sorbitol pathway and of hypothetical regulatory sites for the glucose molecule ("receptors") are briefly discussed.
Diabetes 1976 May
PMID:Further studies on the metabolism of D-glucose anomers in pancreatic islets. 77 24

The direct effects of alloxan on glucose-induced insulin secretion and biosynthesis and the interaction of alloxan and D-glucose anomers were studied in vitro by use of isolated islets from rat pancreas. Islets were pretreated by incubation for five minutes in media containing alloxan (0.2 mg./ml.) alone or alloxan with either the alpha or beta anomer of D-glucose (3 mg./ml.). After washing, batches of five islets were incubated in the medium supplemented with glucose (1.8 mg./ml.) for 60 minutes to observe insulin secretion and for 90 minutes to observe insulin biosynthesis. Prior exposure to alloxan alone produced marked inhibition of subsequent glucose-induced insulin secretion and biosynthesis. A significantly greater protection against these inhibitory effects of alloxan was observed by using the alpha anomer of D-glucose than the beta anomer. The anomeric preference of D-glucose for protecting islet cells from the inhibitory effect of alloxan on glucose-induced insulin secretion and biosynthesis was similar to that for triggering insulin secretion. Possible mechanisms of the inhibitory effect of alloxan and the protective effect of D-glucose anomers in connection with those of other sugars are discussed. It is suggested that a glucoreceptor, stereospecific to the alpha anomer of D-glucose, may exist for both insulin secretion and biosynthesis.
Diabetes 1976 Jul
PMID:Interaction of alloxan and anomers of D-glucose on glucose-induced insulin secretion and biosynthesis in vitro. 77 25

The artificial beta cell is a Glucose Controlled Insulin (and dextrose) Infusion System (GCIIS) for maintaining normoglycemia in diabetic conditions and other disturbances of metabolism. The insulin and dextrose infusion rates are calculated by a microcomputer according to the static glucose concentration (proportional control) and to its rate of change (dynamic control). The algorithms controlling the computer can be adapted to the subjects' requirements. It has already been shown, that the artificial beta cell is able to maintain blood sugar values in diabetics within physiological ranges during the course of the day. In our present study we examined the response of the artificial beta cell using a 100 gm oral glucose load in severe diabetics. The first type of control algorithms applied effected a rather small initial insulin infusion following OGTT in 8 juvenile diabetics connected with the artificial beta cell. The glucose responses thus obtained were similar to latent diabetes. In contrast, when the computer was controlled by the second type of algorithms with a more responsive dynamic control and a consequently higher initial insulin infusion, in one diabetic OGTT was fully normalized, whereas an improvement was achieved in another diabetic patient. Furthermore it was shown that control algorithms must be varied individually, depending on residual beta cell function and glucose regulatory mechanisms.
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PMID:Attempts at perfect normalization of glucose tolerance test of severe diabetics by artificial beta cell. 78 30

Some of the acute metabolic derangements of unstable diabetes have been discussed. The management of patients undergoing surgical operations has also been considered. No problems are usually encountered in diabetic patients treated with diet alone or with oral hypoglycaemic compounds, although chlorpropamide may need to be stopped sometime before operation. Patients receiving insulin therapy should be stabilised pre-operatively on a regimen which will allow more flexible management during operation and in the postoperative period; this can be readily performed by placing the patient on soluble insulin and giving spaced dosages. Other routines may be used for minor procedures. Adequate supplies of carbohydrate should be given in the form of intravenous dextrose and under no circumstances should oral glucose be given in the 6 hours before operation.
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PMID:The emergency management of diabetes mellitus. 80 20

A preparation of plasma membranes isolated from human omental lipocytes is composed of about 15 major polypeptide components including three major glycoproteins with an apparent molecular weight range from 100000 to 23 000, as determined by sodium dodecyl sulfate - polyacrylamide gel electrophoresis. Extraction of this membrane preparation with sodium iodide or 2,3-dimethylmaleic anhydride solubilized 50 and 70% of the membrane protein, respectively, resulting from the extensive extraction of protein from all but two of the major membrane polypeptide components. This removal of protein did not affect the membrane's stereospecific D-glucose-uptake activity but did reduce its total specific [125I]insulin-binding activity by 46-67%. The binding of [125I]insulin to its specific receptor on lipocyte plasma membranes was detected at physiologic concentrations of the hormone and could be competitively displaced by increasing concentrations of native insulin. The kinetic behaviour of this reaction was approximated by Scatchard analysis, and both the affinity and binding capacity of the plasma membrane for insulin were increased at lower temperatures. These results suggest that D-glucose transport in human adipose tissue is mediated by an intrinsic component of the hydrophobic structure of the lipocyte plasma membrane, and represent a partial purification of this component. In addition, these studies demonstrate and characterize the binding of insulin to the plasma membrane isolated from human lipocytes. A quantitative study of this binding reaction may provide further understanding of the mechanisms underlying the decreased insulin responsiveness characteristic of human diabetes.
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PMID:D-Glucose uptake and insulin binding by the human adipose cell plasma membrane as a function of its polypeptide composition. 84 81

Hemoglobin AIc is a minor component of normal adult erythrocytes whose concentration is elevated approximately 2-fold in patients with diabetes mellitus. Previous work suggested that the unique structural feature of hemoglobin AIc is the presence of a low molecular weight sugar moiety at the NH2-terminal valine of the beta chain. In this study the structure of the carbohydrate moiety and the nature of its linkage of the beta chain were investigated. Enzymatic digestion of borohydride-reduced betaAIc chains followed by ion exchange chromatography led to the isolation of two distinct NH2-terminal glycovalylhistidines. Comparison of these glycodipeptides with synthetic glycovalylhistidines by thin layer chromatography, gas-liquid chromatography, and proton magnetic resonance spectroscopy gave direct evidence that the naturally derived materials correspond to glucitol and mannitol valylhistidines. Model reactions showed that glucose and mannose react with valine under mild conditions to form an adduct which upon sodium borohydride reduction yields in both cases glucitol and mannitol valines. This suggests a common intermediate, 1-deoxy-1-(N-valyl)fructose, for both reactions. From these studies we conclude that hemoglobin AIc has, as the NH2 terminus of the beta chain, 1-deoxy-1-(N-valyl)fructose. The possible biosynthetic pathways of hemoglobin AIc are discussed.
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PMID:Structure of carbohydrate of hemoglobin AIc. 85 40

An extracorporeal "closed-loop" system has been employed to maintain glycemia in the normal range during consumption of meals in nine insulin-treated diabetics. This artificial pancreas system incorporated continuous blood glucose monitoring (0.05 ml. per minute, delay time 90 seconds), a computer programed to respond to glycemia, and a hormone delivery system. Intravenous insulin delivery rates were determined by control parameters responsive to both glucose concentration and its rate of change. Because insulin-dependent diabetics often defend themselves poorly against hypoglycemia (in some cases due to inadequate glucagon responses), the instrument was also programed for exogenous glucagon delivery. A priori selection of ideal parameters for insulin and glucagon delivery for each individual is not yet possible. Consequently, when the parameters were used for the first time on each subject, they were varied over a reasonable range. This approach resulted in a corresponding variety of glycemic responses, the average of which characterized a set of initial parameters that is generally applicable. Appropriate control parameters are presented that successfully prevented hypoglycemia. Glucagon delivery directly related to glycemia appeared sufficient for this purpose, thus obviating the need for dextrose administration. This system provides a technique for complete normalization of blood glucose concentration in the types of diabetics tested, during both fed and interprandial periods. It has yielded insights essential to the development of more sophisticated future devices.
Diabetes 1977 Jul
PMID:Normalization of glycemia in diabetics during meals with insulin and glucagon delivery by the artificial pancreas. 87 73

The quantity and distribution of glycogen has been studied in 86 placentae from the last trimester of pregnancy and 8 of 8 to 16 weeks gestational age. In the first trimester glycogen concentrations were high, between 4-5 to 6-5 mg/g of blood-free tissue, but from about 12 weeks to term the concentrations were within a narrow range around 1-5 mg/g. The level did not deviate appreciably from normal in a range of clinical conditions: diabetes, intrauterine growth retardation, pre-eclampsia or acute fetal distress, and was unaffected by the length of labour and whether or not the mother had been given an infusion of dextrose. Nor was it affected by a wide range of glucose concentrations in the maternal and fetal plasma and in the placental tissue itself or by insulin concentrations in either circulation. After the first few weeks of pregnancy glycogen in the placenta was shown to be restricted to the vicinity of major fetal blood vessels. Here it may be presumed to act as an energy reserve for vasomotor activity. All the evidence suggests that any importance placental glycogen may have is likely to be local, in relation to the placental vessels; a more general role, as an emergency energy source for the fetus, seems unlikely.
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PMID:Placental glycogen. 94 72

A large number of individuals currently diagnosed as having diabetes mellitus are asymptomatic. In order to provide rational therapy for this patient population, it is necessary to focus upon the differences between these patients and the classic prototypes with polyuria and weight loss, who require insulin for survival. Patients with asymptomatic diabetes do not need insulin for survival, and, by definition, they do not need it to alleviate symptoms. They tend to be middle-aged and overweight, but they can be young and thin. Their degree of hyperglycemia is moderate, often indistinguishable from that of normal individuals in their day-to-day existence. Indeed, they can often be differentiated from normal persons only on the basis of their blood glucose response to the stress of a large dextrose challenge; in this regard, the potential problem of over-diagnosing diabetes has been discussed. Since the major problem facing patients with asymptomatic diabetes is accelerated atherogenesis, the therapeutic approach must be based upon efforts to delay or prevent the onset of vascular disease. It has yet to be shown that any therapeutic intervention helps such patients, but an argument has been made in support of the following goals in subjects with asymptomatic diabetes whose fasting blood glucose level is less than 170 mg/100 ml: (1) stop smoking, (2) control hypertension, (3) attain ideal body weight, and (4) maintain blood triglyceride and cholesterol levels well within normal limits. Attempts to lower blood glucose with either insulin or oral agents do not seem indicated in the majority of patients within this defined diabetic population.
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PMID:Treatment of asymptomatic diabetes mellitus. 97 61


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