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)

The aim of the present study was to monitor clinical, microbiological, medical, and immunological effects of non-surgical periodontal therapy in diabetics and healthy controls. 20 IDDM (insulin dependent, n = 7) or NIDDM (non-insulin dependent, n = 13) diabetic patients (median duration 11.5 years, range of HbA1C: 4.4-10.6%) with moderate to advanced periodontal disease and 20 matched healthy control patients, were subjected to supragingival pretreatment and subsequent subgingival therapy. Periodontal examinations (API, PBI, BOP, PPD, PAL), microbiological examinations (culture), medical routine examinations, and immunological examinations (oxidative burst response of PMNs to TNF-alpha and FMLP) were performed at baseline, 2 weeks after supragingival, and 4 months after subgingival therapy. 4 months after completion of non-surgical therapy, the following compared to baseline significant (p < or = 0.05) changes (delta) of clinical parameters (median) were found in diabetic patients versus control patients: deltaAPI (30.4% versus 36.3%), deltaPBI (22.9% versus 24.2%), deltaBOP (39.5% versus 46.9%). The median % per patient of pockets with PPD > or = 4 mm decreased from 41.9% to 28.3% in diabetics, and from 41.6% to 31.8% in controls. Microbiologically, similar reductions of periopathogenic bacteria were found in diabetics and controls. Neither periodontal data nor the oxidative burst response of PMNs showed any significant difference (p > 0.05) between diabetics and control patients. In this study, periodontal therapy had no significant influence on medical data of diabetics. In conclusion, this study indicates that metabolically well-controlled diabetics might respond to non-surgical periodontal therapy as well as healthy control patients.
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PMID:Healing response to non-surgical periodontal therapy in patients with diabetes mellitus: clinical, microbiological, and immunologic results. 949 10

The prevalence of obesity is increasing rapidly in all age groups in most EU-countries and is one of the fastest growing epidemics, now affecting 10-40% of the adult population. Obesity increases the risk of serious co-morbidities such as type 2 diabetes, cardiovascular disease, certain cancers and reduced life expectancy, and these complications may account for 5-10% of all health costs in EU countries. The risk of diabetes is particularly increased by obesity, and 80-95% of the increase in diabetes can be attributed to obesity and overweight with abdominal fat distribution. There is robust evidence from cross-sectional and longitudinal studies to support that an energy-dense, high fat diet and physical inactivity are independent risk factors for weight gain and obesity. Furthermore, interaction between dietary fat and physical fitness determine fat balance, so that the obesity promoting effect of a high fat diet is enhanced in susceptible subjects, particularly in sedentary individuals with a genetic predisposition to obesity. Ad libitum consumption of diets low in fat and high in protein and complex carbohydrates, with a low glycaemic index, contributes to the prevention of weight gain in normal weight subjects. It also causes a spontaneous weight loss of 3-4 kg in overweight subjects, and has beneficial effects on risk factors for diabetes and CVD. To prevent obesity and diabetes there are grounds for recommending the combination of increasing daily physical activity level to a PAL-value of at least 1.8 and reducing dietary fat content to 20-25 energy-% in sedentary subjects, and to 25-35% in more physically active individuals.
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PMID:Healthy lifestyles in Europe: prevention of obesity and type II diabetes by diet and physical activity. 1168 45

Glucose-dependent insulinotropic polypeptide (GIP) is a physiological insulin releasing peptide. We have developed two novel fatty acid derivatized GIP analogues, which bind to serum albumin and demonstrate enhanced duration of action in vivo. GIP(Lys(16)PAL) and GIP(Lys(37)PAL) were resistant to dipeptidyl peptidase IV (DPP IV) degradation. In vitro studies demonstrated that GIP analogues retained their ability to activate the GIP receptor through production of cAMP and to stimulate insulin secretion. Intraperitoneal administration of GIP analogues to obese diabetic (ob/ob) mice significantly decreased the glycemic excursion and elicited increased and prolonged insulin responses compared to native GIP. A protracted glucose-lowering effect was observed 24 h following GIP(Lys(37)PAL) administration. Once a day injection for 14 days decreased nonfasting glucose, improved glucose tolerance, and enhanced the insulin response to glucose. These data demonstrate that fatty acid derivatized GIP peptides represent a novel class of long-acting stable GIP analogues for therapy of type 2 diabetes.
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PMID:GIP(Lys16PAL) and GIP(Lys37PAL): novel long-acting acylated analogues of glucose-dependent insulinotropic polypeptide with improved antidiabetic potential. 1645 Oct 70

Glucose dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone with therapeutic potential for type 2 diabetes due to its insulin-releasing and antihyperglycaemic actions. However, development of GIP-based therapies is limited by N-terminal degradation by DPP IV resulting in a very short circulating half-life. Numerous GIP analogues have now been generated exhibiting DPP IV resistance and extended bioactivity profiles. In this study, we report a direct comparison of the long-term antidiabetic actions of three such GIP molecules, N-AcGIP, GIP(Lys(37)PAL) and N-AcGIP(Lys(37)PAL) in obese diabetic (ob/ob) mice. An extended duration of action of each GIP analogue was demonstrated prior to examining the effects of once daily injections (25nmolkg(-1) body weight) over a 14-day period. Administration of either N-AcGIP, GIP(Lys(37)PAL) or N-AcGIP(Lys(37)PAL) significantly decreased non-fasting plasma glucose and improved glucose tolerance compared to saline treated controls. All three analogues significantly enhanced glucose and nutrient-induced insulin release, and improved insulin sensitivity. The metabolic and insulin secretory responses to native GIP were also enhanced in 14-day analogue treated mice, revealing no evidence of GIP-receptor desensitization. These effects were accompanied by significantly enhanced pancreatic insulin following N-AcGIP(Lys(37)PAL) and increased islet number and islet size in all three groups. Body weight, food intake and circulating glucagon were unchanged. These data demonstrate the therapeutic potential of once daily injection of enzyme resistant GIP analogues and indicate that N-AcGIP is equally as effective as related palmitate derivatised analogues of GIP.
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PMID:Evaluation of the antidiabetic activity of DPP IV resistant N-terminally modified versus mid-chain acylated analogues of glucose-dependent insulinotropic polypeptide. 1685 46

Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone secreted by endocrine K-cells in response to nutrient absorption. This study has utilised numerous well-characterised dipeptidyl peptidase IV-resistant GIP analogues to evaluate the glucagonotropic actions of GIP in Wistar rats and isolated rat islets. Intraperitoneal administration of GIP analogues (25 nmol/kg body weight) in combination with glucose had no effect on circulating glucagon concentrations compared to controls in Wistar rats. However, plasma glucose concentrations were significantly (p<0.05 to p<0.001) lowered by the GIP-receptor agonists, N-AcGIP, GIP(Lys37)PAL and N-AcGIP(Lys37)PAL. The GIP antagonist, (Pro3)GIP, caused a significant (p<0.05) reduction in glucagon levels following concurrent administration with saline in Wistar rats. In isolated rat islets native GIP induced a significant (p<0.01) enhancement of glucagon release at basal glucose concentrations, which was completely annulled by (Pro3)GIP. Furthermore, glucagon release in the presence of GLP-1, GIP(Lys37)PAL, N-AcGIP(Lys37)PAL and (Pro3)GIP was significantly (p<0.05 to p<0.001) decreased compared to native GIP in isolated rat islets. These data indicate a modest effect of GIP on glucagon secretion from isolated rat islets, which was not observed in vivo. However, the GIP agonists N-AcGIP, GIP(Lys37)PAL and N-AcGIP(Lys37)PAL had no effect on glucagon release demonstrating an improved therapeutic potential for the treatment of type 2 diabetes.
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PMID:Effects of gastric inhibitory polypeptide (GIP) and related analogues on glucagon release at normo- and hyperglycaemia in Wistar rats and isolated islets. 1816 84

Xenin-25, a K-cell derived peptide co-secreted with glucose-dependent insulinotropic polypeptide (GIP), has recently been shown to have glucose homeostatic actions and potentiate the insulinotropic effect of GIP. However, the biological actions of xenin-25 are brief due to rapid metabolism, yet little is known regarding enzymatic degradation of this peptide. Therefore, the present study has fully characterised the plasma enzymatic degradation products of xenin-25. We have also generated a novel acylated xenin-25 analogue, xenin-25(Lys(13)PAL), and evaluated its stability, biological action profile and therapeutic applicability compared to the native peptide. In contrast to xenin-25, xenin-25(Lys(13)PAL) was completely resistant to plasma enzyme degradation. Insulinotropic responses of xenin-25(Lys(13)PAL) in clonal beta-cells were similar to native xenin-25, moreover xenin-25(Lys(13)PAL) significantly (p<0.05 to p<0.001) potentiated the insulin releasing action of (D-Ala(2))GIP. When administered together with glucose to normal mice, the glycaemic excursion was significantly (p<0.05) less and overall insulin secretory effect significantly (p<0.05) greater for xenin-25(Lys(13)PAL) when compared to xenin-25 mice. Glucose-lowering and insulin releasing effects of both peptides was less prominent in high fat fed mice and ob/ob mice. However, xenin-25 significantly (p<0.05) augmented the glucose-lowering action of (D-Ala(2))GIP in both groups of mice. Similarly, xenin-25(Lys(13)PAL) potentiated (p<0.05) the gluco-regulatory effect of (D-Ala(2))GIP. Overall, these data indicate that palmitate-derivatised analogues of xenin-25 represent a novel class of GIP potentiator drugs for possible type 2 diabetes therapy.
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PMID:Degradation, insulin secretion, glucose-lowering and GIP additive actions of a palmitate-derivatised analogue of xenin-25. 2256 Oct 48

Studies initiated 30 years ago emphasized that dilute blood clot lysis time was longer in obese diabetic patients than in normal weight diabetics. It was also later reported that when compared to obese women with gluteal and femoral adiposity, the age matched men with abdominal obesity displayed a more delayed clot lysis, higher triglyceride levels and higher cholinesterase activity, as well as more increased concentration of plasminogen activator inhibitor-1 (PAL-1). According to authors' investigations and data in the literature, impaired fibrinolysis in overweight hypertriglyceridemic subjects are mainly due to increased plasma levels of coagulation factor XIII and PAI-1. It could also be demonstrated that plasma clotting factors VII and VIII activities as well as plasma fibrinogen and von Willebrand factor levels were higher in patients with type 2 diabetes and abdominal obesity than in diabetics without obesity. Such findings are supporting data in the literature, insisting on the pathogenic relevance of intraabdominal obesity and of the subsequently enhanced release of fatty acids and of proinflammatory cytokines in the portal flow. Surprisingly anticoagulant plasma proteins C and S levels were found to be increased in overweight and hyperlipidemic patients considered to be at risk for thrombotic complications. Recent data in the literature had however demonstrated that circulating protein C zymogen acquires anticoagulant activity only after its binding to specific receptors on endothelial cell membrane, while proinflammatory cytokines may disrupt this activating interaction with vascular endothelia.
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PMID:Thrombotic tendency in diabetes mellitus. Revisiting and revising a study initiated 30 years ago. 2332 54

Glucagon-like peptide 1 (GLP-1) is a hormone and a growth factor. GLP-1 mimetics are currently on the market as treatments for type 2 diabetes. They also have shown neuroprotective properties in animal models of neurodegenerative disorders. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in animal models of Parkinson's disease (PD), and a first clinical trial in PD patients showed promising results. (Val8)GLP-1-glu-PAL is a new GLP-1 analogue which has a longer biological half-life than exendin-4. We previously showed that (Val8)GLP-1-glu-PAL has neuroprotective properties. Here we tested the drug in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP was injected (30mg/kg i.p.) along with (Val8)GLP-1-glu-PAL (25nmol/kg i.p.) once-daily for 8 days. (Val8)GLP-1-glu-PAL showed good effects in preventing the MPTP-induced motor impairment (Rotarod, open field locomotion, swim test), reduction in tyrosine hydroxylase levels (dopamine synthesis) in the substantia nigra, a reduction of activated caspase 3 levels, of TUNEL positive cell numbers, of the pro-apoptotic signaling molecule BAX and an increase in the growth signaling molecule Bcl-2. The results demonstrate that (Val8)GLP-1-glu-PAL shows promise as a novel treatment of PD.
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PMID:Neuroprotective effects of (Val8)GLP-1-Glu-PAL in the MPTP Parkinson's disease mouse model. 2618 89

Parkinson's disease (PD) is a chronic neurodegenerative disease, and there is no cure for it at present. Recent research has indicated a link between type 2 diabetes mellitus (T2DM) and PD, which suggested that a treatment to improve insulin resistance for T2DM may be useful for PD patients. Glucose-dependent insulinotropic polypeptide (GIP) belongs to the incretin hormone family, which can promote insulin release and improve insulin resistance. Several GIP analogues have been developed as potential treatments for T2DM. In the present study, a novel long-lasting GIP analogue, D-Ala2-GIP-glu-PAL, has been tested in an acute PD mouse model induced by four 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intraperitoneal injections. D-Ala2-GIP-glu-PAL treatment (25 nmol/kg ip.) for 7 days after MPTP treatment improved the locomotor and exploratory activity of mice, and improved bradykinesia and movement balance of mice. D-Ala2-GIP-glu-PAL treatment also restored tyrosine hydroxylase (TH) positive dopaminergic neuron numbers in the substantia nigra and TH levels in the striatum. D-Ala2-GIP-glu-PAL also reduced the chronic inflammation response as seen in astrocyte and microglia activation in the substantia nigra pars compacta (SNpc). D-Ala2-GIP-glu-PAL reversed the reduction of synapse numbers (synaptophysin levels), decreased the ratio of growth factor and apoptosis signaling molecules Bax/Bcl-2, and improved the decrease of p-CREB(S133) growth factor signaling in the substantia nigra. Therefore, D-Ala2-GIP-glu-PAL promotes cell survival of dopaminergic neuron in the SNpc by activating the cAMP/PKA/CREB growth factor second messenger pathway that also inhibits apoptosis. The present results demonstrate that D-Ala2-GIP-glu-PAL shows promise as a novel treatment of PD.
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PMID:Neuroprotective effects of a GIP analogue in the MPTP Parkinson's disease mouse model. 2645 62

Ablation of glucagon receptor signaling represents a potential treatment option for type 2 diabetes (T2DM). Additionally, activation of glucose-dependent insulinotropic polypeptide (GIP) receptor signaling also holds therapeutic promise for T2DM. Therefore, this study examined both independent and combined metabolic actions of desHis(1)Pro(4)Glu(9)(Lys(12)PAL)-glucagon (glucagon receptor antagonist) and d-Ala(2)GIP (GIP receptor agonist) in diet-induced obese mice. Glucagon receptor binding has been linked to alpha-helical structure and desHis(1)Pro(4)Glu(9)(Lys(12)PAL)-glucagon displayed enhanced alpha-helical content compared with native glucagon. In clonal pancreatic BRIN-BD11 beta-cells, desHis(1)Pro(4)Glu(9)(Lys(12)PAL)-glucagon was devoid of any insulinotropic or cAMP-generating actions, and did not impede d-Ala(2)GIP-mediated (P<0.01 to P<0.001) effects on insulin and cAMP production. Twice-daily injection of desHis(1)Pro(4)Glu(9)(Lys(12)PAL)-glucagon or d-Ala(2)GIP alone, and in combination, in high-fat-fed mice failed to affect body weight or energy intake. Circulating blood glucose levels were significantly (P<0.05 to P<0.01) decreased by all treatments regimens, with plasma and pancreatic insulin elevated (P<0.05 to P<0.001) in all mice receiving d-Ala(2)GIP. Interestingly, plasma glucagon concentrations were decreased (P<0.05) by sustained glucagon inhibition (day 28), but increased (P<0.05) by d-Ala(2)GIP therapy, with a combined treatment resulting in glucagon concentration similar to saline controls. All treatments improved (P<0.01) intraperitoneal and oral glucose tolerance, and peripheral insulin sensitivity. d-Ala(2)GIP-treated mice showed increased glucose-induced insulin secretion in response to intraperitoneal and oral glucose. Metabolic rate and ambulatory locomotor activity were increased (P<0.05 to P<0.001) in all desHis(1)Pro(4)Glu(9)(Lys(12)PAL)-glucagon-treated mice. These studies highlight the potential of glucagon receptor inhibition alone, and in combination with GIP receptor activation, for T2DM treatment.
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PMID:Glucagon receptor antagonist and GIP agonist combination for diet-induced obese mice. 2709 30


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