Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The higher prevalence of diabetes for cataracts as a component of the multifactorial genesis of age-related cataracts has been proven in several epidemiological studies. Most of these results identified diabetes as a highly significant risk factor for cataracts in older diabetic males and females. The increased cataract risk of diabetics then decreases after the age of 65 years and is related to different types of opacity. In addition to the sorbitol pathway, diabetic hyperglycaemia causes increased formation of glucose-derived advanced glycation cytotoxic end-products. In connection with these specific pathological changes, the crucial role of the lens epithelium with respect to cataractogenesis is emphasised in several studies. The results of our own prospective clinical study proved the significantly lower mean cell density in type II diabetics compared with eyes from non-diabetics. Together with the other determined morphological cell characteristics, this result seems to be due to the cataractogenic influence of diabetic metabolic disorders on the lens There are some indications for the primary cataractogenic importance of the lens epithelium in type II diabetes.
 ...
PMID:[Is diabetes in the elderly patient a risk factor for cataracts?]. 1149 Jul 49

Dyslipidemia, a major risk factor for cardiovascular disease, may be directly linked to diabetic hyperglycemia and insulin resistance. An appropriate dyslipidemic animal model that has diabetes would provide an important tool for research on the treatment of diabetic dyslipidemia. Ten days of high fat feeding in golden Syrian hamsters resulted in a significant increase in insulin resistance and baseline serum lipid levels accompanied by a pronounced dyslipidemia. Thirteen days of treatment with fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARalpha) selective agonist, produced a dose-dependent decrease in serum lipid levels. The pattern observed was characterized by lowered very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) and raised high-density lipoprotein (HDL) cholesterol in a fashion similar to that seen in man. Diabetic conditions were also significantly improved by fenofibrate with a normalization of impaired glucose tolerance and an improvement of insulin sensitivity during an oral glucose tolerance test. These data suggest that fenofibrate may correct not only the dyslipidemia but also the insulin resistance caused by a high fat diet, and the high fat fed hamster may be a good animal model for research on the treatment of diabetic dyslipidemia with PPARalpha selective agonists.
 ...
PMID:High fat fed hamster, a unique animal model for treatment of diabetic dyslipidemia with peroxisome proliferator activated receptor alpha selective agonists. 1156 59

To determine whether enzymatic p53 glycosylation leads to angiotensin II formation followed by p53 phosphorylation, prolonged activation of the renin-angiotensin system, and apoptosis, ventricular myocytes were exposed to levels of glucose mimicking diabetic hyperglycemia. At a high glucose concentration, O-glycosylation of p53 occurred between 10 and 20 min, reached its peak at 1 h, and then decreased with time. Angiotensin II synthesis increased at 45 min and 1 h, resulting in p38 mitogen-activated protein (MAP) kinase-driven p53 phosphorylation at Ser 390. p53 phosphorylation was absent at the early time points, becoming evident at 1 h, and increasing progressively from 3 h to 4 days. Phosphorylated p53 at Ser 18 and activated c-Jun NH(2)-terminal kinases were identified with hyperglycemia, whereas extracellular signal-regulated kinase was not phosphorylated. Upregulation of p53 was associated with an accumulation of angiotensinogen and AT(1) and enhanced production of angiotensin II. Bax quantity also increased. These multiple adaptations paralleled the concentrations of glucose in the medium and the duration of the culture. Myocyte death by apoptosis directly correlated with glucose and angiotensin II levels. Inhibition of O-glycosylation prevented the initial synthesis of angiotensin II, p53, and p38-MAP kinase (MAPK) phosphorylation and apoptosis. AT(1) blockade had no influence on O-glycosylation of p53, but it interfered with p53 phosphorylation; losartan also prevented phosphorylation of p38-MAPK by angiotensin II. Inhibition of p38-MAPK mimicked at a more distal level the consequences of losartan. In conclusion, these in vitro results support the notion that hyperglycemia with diabetes promotes myocyte apoptosis mediated by activation of p53 and effector responses involving the local renin-angiotensin system.
Diabetes 2001 Oct
PMID:Hyperglycemia activates p53 and p53-regulated genes leading to myocyte cell death. 1157 21

Excessive glucose production by the liver contributes significantly to diabetic hyperglycemia. The enzyme system glucose-6-phosphatase plays a key role in regulating hepatic glucose production and therefore its inhibition is a potential therapeutic target for the correction of hyperglycemia. It has previously been shown that sulfated steroids, such as estrone sulfate and dehydroepiandrosterone sulfate, inhibit the glucose-6-phosphatase system in vitro, principally through inhibition of endoplasmic reticulum glucose-6-phosphate transport. We report here that in the obese/diabetic ob/ob mouse model, orally administered estrone sulfate reduces the abnormally elevated hepatic glucose-6-phosphatase enzyme activity and enzyme protein levels that are characteristic in the ob/ob mouse, and that this reduction is associated with normalization of blood glucose levels. Other sulfated and non-sulfated steroids also reduced, to a lesser extent, glucose-6-phosphatase enzyme activity - with the exception of dehydroepiandrosterone sulfate, which had no apparent effect on this system in ob/ob mice. Estrone sulfate is therefore an effective antihyperglycemic agent in ob/ob mice, and the glucose-6-phosphatase system can be successfully targeted for the therapeutic management of hyperglycemia in this animal model of non-insulin-dependent diabetes mellitus.
 ...
PMID:The antihyperglycemic effect of estrone sulfate in genetically obese-diabetic (ob/ob) mice is associated with reduced hepatic glucose-6-phosphatase. 1175 57

The role of fat in the aetiology of insulin resistance and type 2 diabetes has been re-considered in the present review. This is because of the questions raised by recent created mouse models imitating human lipodystrophy diabetes. It appears that hepatic steatosis, which is shared by both lipodystrophy and most if not all obesity patients, may play a key role in the pathogenesis of insulin resistance and type 2 diabetes despite the fact that lipodystrophy is an extreme state and occurs more rarely than obesity. The possible link between lipid and glucose metabolisms via peroxisome activity has been examined and its role in determining hyperglycaemia is suggested. Moreover, new avenues towards a better understanding of insulin resistance at the genomic level have also been proposed. It appears that one of the most fundamental biological phenomena, fuel selection, may underlie the causes of diabetic hyperglycaemia and perplex the role of fat in the aetiology of insulin resistance.
Diabetes Metab Res Rev
PMID:The role of increased liver triglyceride content: a culprit of diabetic hyperglycaemia? 1192 13

Folium mori, the leaves of Morus alba L., has traditionally been used for the treatment of diabetic hyperglycemia. It has been shown to induce enhanced NOS expression in the hypothalamus of rats with streptozotocin (STZ)-induced diabetes. In the present study, the effect of Folium mori on the expression of nitric oxide synthase (NOS) in the hypothalamus of STZ-induced diabetic rats was investigated via nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry. Enhanced NAPDH-d expression was detected in the paraventricular nucleus, ventromedial hypothalamic nucleus, and lateral hypothalamic area of the hypothalamus in the STZ-induced diabetes group. Administration of the aqueous extract of Folium mori to rats with STZ-induced diabetes resulted in decreased NADPH-d positivity. These results suggest that Folium mori treatment is effective in curbing the desire for food under diabetic conditions via modulation of NO expression in the hypothalamus.
 ...
PMID:Administration of Folium mori extract decreases nitric oxide synthase expression in the hypothalamus of streptozotocin-induced diabetic rats. 1241 90

Data derived from animals and humans suggest that the onset of diabetes is associated with hemodynamic changes in the renal circulation leading to increased renal plasma flow (RPF), glomerular capillary hyperfusion, and an increased glomerular transcapillary hydraulic pressure gradient. The duration of diabetes is one of the most important factors in predicting the development of diabetic nephropathy. On the other hand, diabetic nephropathy has been associated with the degree of hyperglycemia; thus, hyperglycemia may therefore contribute to alterations in structure and function of the kidney. In the present paper, we investigated early alterations of renal function in C57BL/KSJ mdb male mice that were injected with sub-diabetogenic doses of STZ. Urinary protein excretion (UPE) increased significantly at 12 and 18-20 days after STZ with a glucose level of 4-6 mm/l; the progressive increase of glycemia was followed by a progressive increase of UPE. In a similar way, urinary nitrite (NO2-) was also significantly increased. Urinary kallikrein excretion started to increase at a level of 4-6 mmol/l blood glucose concentration (BGC) 8 days after administration of STZ, and kidney vascular permeability also increased following the increment of BGC. These results confirm the presence of early modifications of renal function prior to the clinical detection of diabetic hyperglycemia.
 ...
PMID:The development of insulitis and the kallikrein-kinin system. 1248 7

Type 1 diabetic patients depend on insulin replacement therapy. However, chronic hyperglycemia due to failure to maintain proper glycemic control leads to microvascular, macrovascular, and neurological complications. Increased glucose disposal by tissues engineered to overexpress key regulatory genes in glucose transport or phosphorylation can reduce diabetic hyperglycemia. Here we report that differentiated myoblast cells expressing the glucose-phosphorylating enzyme glucokinase (GK) showed a glucose-dependent increase in glucose uptake and utilization in vitro. Transplantation of GK-expressing myotubes into healthy mice did not alter blood glucose levels and recipient mice maintained normoglycemia. After streptozotocin treatment, mice transplanted with GK-expressing myotubes counteracted hyperglycemia, polydipsia, and polyphagia, whereas mice transplanted with control myotubes developed diabetes. Similarly, diabetic mice transplanted with control myotubes remained hyperglycemic. In contrast, transplantation of GK-expressing myotubes into diabetic mice lowered hyperglycemia. These results suggest that the use of genetically engineered muscle cells to express glucokinase may provide a glucose-regulated approach to reduce diabetic hyperglycemia.
 ...
PMID:Glucose-regulated glucose uptake by transplanted muscle cells expressing glucokinase counteracts diabetic hyperglycemia. 1254 44

Complex though integrated hormonal and metabolic changes characterize pregnancy. In the face of progressive decline in insulin action, glucose homeostasis is maintained through a compensatory increase in insulin secretion. This switches energy production from carbohydrates to lipids, making glucose readily available to the fetus. This precise and entangled hormonal and metabolic condition can, however, be disrupted and diabetic hyperglycemia can develop (gestational diabetes). The increase in plasma glucose level is believed to confer significant risk of complications to both the mother and the fetus and the newborn. Moreover, exposition of fetal tissues to the diabetic maternal environment can translate into an increased risk for development of diabetes and/or the metabolic syndrome in the adult life. In women with previous gestational diabetes, the risk of developing type 2 diabetes is greatly enhanced, to the point that GDM represents an early stage in the natural history of type 2 diabetes. In these women, accurate follow-up and prevention strategies are needed to reduce the subsequent development of overt diabetes. This paper will review current knowledge on the modifications occurring in normal pregnancy, while outlining the mechanisms. In this paper, we will review the changes of intermediary metabolism occurring during pregnancy. In particular, we will outline the mechanisms responsible for gestational diabetes; the link between these alterations and associated maternal and neonatal morbidity will be examined.
Diabetes Metab Res Rev
PMID:Intermediate metabolism in normal pregnancy and in gestational diabetes. 1287 3

Type 2 diabetes is preceded by long-standing asymptomatic hyperglycaemia. This prediabetic state is characterised by elevated post-prandial hyperglycaemia and yet normal fasting plasma glucose (FPG). The relationship between abnormal circulating glucose levels and the development of long-term diabetic complications became apparent 70 years ago, soon after the introduction of insulin and the prevention of early death due to ketoacidosis. The main issues regarding diabetes and the various target organs throughout the cardiovascular system, including coronary artery disease (CAD), peripheral vascular disease (PVD), increased intima-media thickness (IMT) and stroke, are as follows: CAD causes much of the serious morbidity and mortality in patients with diabetes, who have a 2- to 4-fold increased risk of CAD; epidemiological evidence confirms an association between diabetes and increased prevalence of PVD; and diabetes induces increased IMT and stroke by adversely affecting cerebrovascular circulation including the carotid artery, akin to its effects in the coronary and lower extremity vasculature. In diabetes, FPG and HbA(1C) are the main parameters of glucose metabolism used to monitor and control hyperglycaemia. Recently, particular emphasis has been placed on post-prandial plasma glucose as a parameter in the metabolic assessment of diabetic patients. Therefore, while addressing the question of hyperglycaemia and its relation to cardiovascular morbidity and mortality, we have to look for the possible mechanisms by which diabetic hyperglycaemia causes these complications. Then, we must examine the evidence on how the main parameters of glucose metabolism correlate with cardiovascular complications. This review addresses these issues.
 ...
PMID:Hyperglycaemia and its relation to cardiovascular morbidity and mortality: has it been resolved? 1470 73


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>