Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seven cytoplasmic enzyme activities were measured in extracts of mononuclear leukocytes (lymphocytes plus monocytes) obtained from 19 type II diabetic humans and 10 healthy control subjects. 6-Phosphofructokinase activity was significantly decreased in cell extracts from diabetics, while other enzyme activities were similar in diabetics and controls. Since the effects of starvation on enzyme activities are sometimes similar to the effects of diabetes, the studies were repeated in 5 control subjects after a 2-day fast. This short period of starvation did not mimic the effect of diabetes on 6-phosphofructokinase activity. The decreased enzyme activity was not correlated with percent specific insulin binding to monocytes in the same cell preparations nor to clinical variables such as obesity or the broad range of fasting plasma glucose values encountered among the diabetics. We conclude that 6-phosphofructokinase activity in mononuclear leukocytes, as in other tissues, may be a marker for a postreceptor lesion associated with the insulin resistance found in type II diabetes mellitus.
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PMID:Impaired 6-phosphofructokinase activity in mononuclear leukocytes from patients with type II diabetes mellitus. 295 96

Many tissues from wild type mice express cytosolic malic enzyme activity and contain two mRNAs (2.0 and 3.1 kilobases (kb)) that encode a single 64-kDa malic enzyme subunit polypeptide. MOD-1 null mutant mice lack cytosolic malic enzyme activity but express 2.5- and 3.6-kb mRNAs that hybridize with wild type malic enzyme cDNAs and are induced in liver by a starvation/carbohydrate refeeding regimen. To investigate the basis of the MOD-1 null mutation, a lambda gt11 cDNA library was constructed using mRNA from the livers of induced MOD-1 null mice as a template. A recombinant phage with a 2-kb insert was isolated by screening with wild type malic enzyme cDNA probes. The subcloned insert exhibited an atypical (non-wild type) restriction pattern and was subjected to sequence analysis. MOD-1 null malic enzyme cDNA contains an internal tandemly duplicated sequence that corresponds to nucleotides 1027-1548 in the coding region of wild type murine malic enzyme cDNA (Bagchi, S., Wise, L. S., Brown, M. L., Bregman, D., Sul, H. S., and Rubin, C. S. (1987) J. Biol. Chem. 262, 1558-1565). An open reading frame is retained throughout the duplicated sequence. The discovery of a 522-nucleotide in-frame duplication accounts for the increased size of MOD-1 null malic enzyme mRNAs and suggests that a variant malic enzyme polypeptide that is 19 kDa larger than the wild type subunit might be found in mutant mice. Western immunoblot analysis disclosed that MOD-1 null liver cytosol contains an 82-kDa protein that is recognized by anti-malic enzyme antibodies. Under stringent conditions, an anti-sense 32P-oligonucleotide that spans the abnormal junction between the reiterated sequences hybridized with the 2.5 and 3.6-kb MOD-1 null malic enzyme mRNAs but failed to form stable complexes with wild type malic enzyme mRNAs. Thus, both MOD-1 null malic enzyme mRNAs contain the duplication deduced from cDNA sequence analyses. The MOD-1 null mutation might originate from an unequal crossover between homologous regions of two different introns in the malic enzyme gene, thereby causing the duplication of one or more exons.
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PMID:The molecular basis for a cytosolic malic enzyme null mutation. Malic enzyme mRNA from MOD-1 null mice contains an internal in-frame duplication that extends the coding sequence by 522 nucleotides. 334 58

In order to better understand the role of A- and B-cell function in diabetic pregnancy, we studied four groups of pregnant women at week 34-36 of gestation. Seventeen were healthy controls (C), 24 had gestational diabetes (GD), 16 had type 2 diabetes (NIDD) and 37 had type 1 diabetes (IDD). At times -20, 0, 20, 30, 45, 60, 90 and 120 min from the beginning of a 30 min infusion of 30 g of arginine intravenously, plasma glucose, glucagon (IRG) and C-peptide (CPR) were measured. Plasma glucose was higher in diabetic than in control subjects. IRG values were also higher in the GD and the NIDD women. CPR values were similar to, or slightly higher than control values in the GD and the NIDD and were much lower in the IDD women. All three variables increased during the arginine infusion in all groups, with the exception that CPR remained unchanged in the IDD. The CPR/IRG molar ratio was similar in control, GD and NIDD women; in the IDD, it was much smaller than in the other groups and was not affected by arginine. In all the diabetic patients, IRG was negatively correlated with the maternal weight gain and in the IDD IRG was positively correlated with the increase in the insulin need and with the CPR levels. In conclusion diabetes appeared to enhance the A-cell function also in pregnancy, possibly impairing the 'facilitated anabolism' and stressing the 'accelerated starvation' which are typical of normal pregnancy. Glucagon was confirmed as one possible determinant of the insulin resistance seen in diabetic pregnancy.
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PMID:Endocrine pancreatic function in insulin-dependent diabetic pregnant women. 353 67

Patients with type II diabetes mellitus (type II DM patients) are characteristically obese, hyperinsulinemic, and non-ketosis prone. Recently, we have encountered several obese type II DM patients with either diabetic ketoacidosis or significant ketonuria after insulin withdrawal. There was no evidence of infection, stress, or starvation to explain their ketonuria. Therefore, we assessed serum connecting peptide (C-peptide) response to oral glucose in 14 obese, insulin-treated type II DM patients: 6 with and 8 without episodes of spontaneous ketonuria. The group presenting with ketonuria had low to absent basal and stimulated serum C-peptide responses. The nonketonuric group had higher basal C-peptide (P less than 0.01) concentrations that increased significantly (P less than 0.001) after oral glucose compared with those of the ketonuric group. Clinical characteristics and biochemical control were similar in both groups. Our findings confirm that obese type II diabetes mellitus is a heterogeneous disease with variable fasting and stimulated C-peptide responses. Spontaneous ketonuria could be a feature in the clinical presentation of the patients especially in the presence of both low fasting and stimulated C-peptide levels. The significance of these findings is unclear but suggests individualization in the management of type II DM patients and cautious withdrawal of insulin therapy in such patients. Furthermore, serum C-peptide levels alone cannot be recommended to classify patients into either type I or type II diabetes mellitus.
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PMID:Significance of spontaneous ketonuria and serum C-peptide levels in obese type II diabetic patients. 638 58

The antilipolytic effect of insulin in vitro was investigated in conditions known to be associated with resistance to the effect of insulin on glucose metabolism. Human subcutaneous adipose tissue was obtained from 14 obese subjects before and during starvation for 7 days, 12 untreated non-insulin dependent diabetics (NIDDM), 6 untreated insulin dependent diabetics (IDDM), and 10 nonobese control subjects. The tissue was incubated with and without insulin in concentration ranging from 1-10,000 microunits/ml. Responsiveness (maximum effect) and sensitivity to insulin were determined under basal induction conditions, since insulin had a bimodal effect on noradrenaline stimulated lipolysis. Under normal conditions both insulin sensitivity and insulin responsiveness were positively correlated with the basal rate of lipolysis. In obesity, IDDM and NIDDM there were no change in insulin sensitivity or in insulin responsiveness. When the obese subjects were divided into one hyperinsulinemic group (6 individuals) and one group with normal fasting serum insulin levels (7 individuals) a similar antilipolytic effect of insulin was observed in the two groups. During starvation there was a 20-fold increase in insulin sensitivity (p less than 0.01) but no change in insulin responsiveness in femoral fat and only a decrease in responsiveness (p less than 0.01) in abdominal fat. The present data supports the view that antilipolysis in human fat cells is not involved in the insulin resistance seen in obesity, starvation, diabetes and hyperinsulinemia.
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PMID:The antilipolytic effect of insulin in human adipose tissue in obesity, diabetes mellitus, hyperinsulinemia, and starvation. 702 6

Increased energy needs, a reduced synthesis of endogenous substrates and a limited energy yield from exogenous substrates characterize the metabolic dilemma in patients with liver cirrhosis. The metabolic features observed in cirrhosis are highly variable and cannot be considered as clear-cut phenomena. They obviously differ in certain aspects from the metabolic situations known from starvation or type 2 diabetes mellitus. This is not contrary to the idea that cirrhosis may resemble certain aspects of these 'standard' situations. Cirrhosis-induced disturbances in fuel homeostasis cannot be predicted from clinical and biochemical parameters of the disease. Most of the metabolic picture is present at a very early stage of liver disease. Many metabolic features are independent of the clinical course of liver disease, suggesting that they are an early and extra-hepatic manifestation. A better understanding of the variance of cirrhosis-induced alterations in metabolism may come from characterization of the metabolic 'genotype' which adds to disease-related factors in the individual patient.
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PMID:Energy expenditure and substrate metabolism in liver cirrhosis. 812 90

Graphic analyses have been used in the study of physiology as a means to better understand dynamic processes and to visualize the mechanisms of their interactions. A graphic analysis of glucose homeostasis was constructed by considering the main factors that influence glucose dynamics. The analysis is achieved by equating curves representing both the inflow and outflow of glucose from the circulation as dependent upon the serum insulin concentration. The point where these two curves intersect is the steady-state balance for blood glucose exchange and is termed the equilibrium point. With the use of this graphic depiction of glucose homeostasis, it is now possible to study the influence of multiple factors on glucose dynamics. A variety of metabolic states can also be analyzed by reconstructing the effects of the pathophysiology on the form and shape of the curves. Some of the metabolic states that have been analyzed by this technique include starvation, exercise, obesity, type I and type II diabetes mellitus, stress, hypopituitarism, hyperpituitarism, and hyperthyroidism. Although the analyses do not reflect all of the controversial nuances of the field, they do provide a means for a general approach to the study of glucose homeostasis and serve as a methodology that can be extrapolated to many areas of physiological study.
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PMID:Graphic analysis for the study of metabolic states. 871 58

Non-insulin-dependent diabetes mellitus (NIDDM) is one of the most common non-communicable diseases in the world. It has become obvious that NIDDM is the result of a collision between thrifty genes and an affluent society. Genes predisposing to NIDDM might have been survival genes for our ancestors, helping them to store energy during long periods of starvation. When these genes are exposed to a sedentary lifestyle and high caloric intake typical to the Western world, they predispose to obesity and insulin resistance. NIDDM results when beta cells cannot compensate for insulin resistance by increasing insulin secretion. Therefore, at least two inherited defects can be expected in NIDDM, one causing obesity and insulin resistance and the other inability to increase insulin secretion. In reality there may be more inherited defects. It has become quite clear that diabetes cannot simply be divided into NIDDM and insulin-dependent diabetes mellitus (IDDM). The disease is more heterogeneous; unmasking this heterogeneity and identifying new subgroups of diabetes presents a challenge to modern molecular biology.
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PMID:Non-insulin-dependent diabetes mellitus--a collision between thrifty genes and an affluent society. 907 23

Evidence, gained from human studies, is reviewed showing that elevation of plasma FFA levels produce peripheral and probably also hepatic insulin resistance in obese healthy and diabetic subjects. First, plasma FFA levels are elevated in most obese subjects. Second, physiological elevations of plasma FFA inhibit acutely as well as chronically insulin stimulated glucose uptake in a dose dependent fashion. Responsible for this inhibition is a FFA induced defect in insulin stimulated glucose transport and/or phosphorylation which develops after 3-4 hours of raising plasma FFA and a second defect, consisting of inhibition of glycogen synthase, the rate limiting enzyme of glycogen synthesis, which develops after 4-6 hours. FFA induced inhibition of fatty acid oxidation (Randle effect) does not affect insulin stimulated glucose uptake or glycogen synthesis and thus does not cause insulin resistance. Elevated plasma FFA levels also modestly increase insulin suppressed endogenous glucose production (EGP) although this effect has not been found by all investigators. The reasons why it has been difficult to demonstrate unequivocal effects of FFA on EGP include 1) the fact that FFA promote insulin secretion which counteracts its effect on EGP (FFA increase, while insulin decreases EGP); 2) the recognition that FFA induced increase in gluconeogenesis may be compensated by intrahepatic downregulation of EGP (i.e., by a decrease in glycogenolysis). The FFA induced insulin resistance is physiologically important during starvation by preserving carbohydrate for oxidation in the central nervous system and during pregnancy, where the well recognized accelerated starvation pattern provides carbohydrate for the growing fetus. In obesity, however, there is no need to spare carbohydrate and the FFA induced insulin resistance may result in type 2 diabetes and other cardiovascular risk factors.
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PMID:Free fatty acids (FFA), a link between obesity and insulin resistance. 945 Sep 85

Genetic analysis of growth from birth to adulthood shows the existence of a strong genetic component in the variance of size at particular milestones in the growth process, such as height at take-off, at peak velocity and at adulthood. While it is well known that postnatal growth is strongly genetically determined, the importance of genes in normal variations of prenatal growth is less known. Genetic analysis of prenatal growth in human is not an easy problem and weighing the genetic and non-genetic component in intra-uterine growth retardation an almost impossible task. It is now well known that adults who had a low birthweight or who were thin at birth, with a low ponderal index, tend to be insulin resistant and have an increased risk of developing non-insulin-dependent diabetes mellitus later in life. According to the thrifty genotype hypothesis, genes predisposing to type 2 diabetes mellitus are very likely to have been survival genes for our ancestors, helping them to store energy during long periods of starvation. Both epidemiological surveys of adults born after prenatal exposure to exposure to famine and biochemical investigations of insulin resistance in low birthweight children show that the association between a low birthweight and an increased risk of developing type 2 diabetes mellitus later in life has a genetic basis. While low birthweight infants have a decreased survival probability in infancy, having a small baby may have been a selective advantage during long periods of starvation. This could explain why the same genetic variants cause low birthweight phenotype and insulin resistance predisposing to non-insulin-dependent diabetes.
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PMID:[Genes and intra-uterine growth retardation]. 985 79


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