Disease relevance of Insulin

• These observational data suggest the need for further study of the relationship between exogenous insulin use and hypertension [1].
• Independent of risk factors, intensive insulin therapy reduced incidence of critical illness polyneuropathy/myopathy (107/212 [50.5%] to 81/208 [38.9%], p = 0.02) [2].
• Because not all moderately obese individuals are at similar risk for developing type 2 diabetes and cardiovascular disease, intensive therapeutic interventions should be addressed to the insulin-resistant subset of this population [3].
• There was a higher rate of hypoglycemia (risk ratio 1.23; 90% confidence interval 1.16, 1.30) but a lower rate of severe hypoglycemia (risk ratio 0.51; 90% confidence interval 0.30, 0.86) with EXU vs. sc insulin [4].
• We hypothesize that modulation of these processes with insulin could improve hepatic structure and function and, therefore, outcome of burned and critically ill patients [5].
• Investigators showed relatively recently that control of hyperglycemia with intensive insulin treatment is associated with improved outcomes for those in the intensive care unit, including patients with severe burns [6].
• Exaggerated insulin secretion may accelerate the progression of liver fibrosis in CHC patients [7].
• In overweight and moderately obese prepubertal children, insulin sensitivity was negatively correlated with SAT and liver fat content [8].
• Reduced insulin signaling in higher animals-rodents and humans-causes glucose intolerance and hyperinsulinemia that progresses to diabetes and shortens the life span of affected individuals [9].
• A proxy measure of insulin secretion strongly predicts changes in body weight and waist circumference over 6 y in adults, especially among those consuming lower-fat diets, which demonstrates the existence of a novel diet-phenotype interaction [10].
• In IR individuals MCh significantly (P < 0.05) ameliorated the delayed onset of insulin action, i.e. the FGU response to hyperinsulinemia [11].
• In adolescents with type 1 diabetes mellitus, glycated haemoglobin and insulin requirements were significantly lower in the CSII groups; no data were available on hypoglycaemic events [12].

Psychiatry related information on Insulin

• Insulin treatment improved metabolic efficiency during exercise, but did not increase maximum exercise capacity and spontaneous physical activity [13].
• Regression models were established to describe associations between fatness, fitness and physical activity and measures of insulin sensitivity (whole-body, fat and liver) as outcomes [14].

Chemical compound and disease context of Insulin

• The addition of low-dose rosiglitazone to insulin therapy is an effective and well-tolerated treatment option for patients with type 2 diabetes mellitus who continue to have poor glycemic control despite administration of exogenous insulin as monotherapy [15].
• Brothers of PCOS women are characterised by decreased insulin sensitivity and glucose tolerance, as well as hypercoagulability, independently of obesity [16].
• Nocturnal variations of EGP and Rd explain the reduced incidence of hypoglycemia and lower fasting glucose levels reported for insulin glargine compared with human NPH insulin [17].
• Recent results show that metformin-induced activation of AMPK disrupts crosstalk between insulin/IGF-1 receptor and GPCR signaling in pancreatic cancer cells and inhibits the growth of these cells in xenograft models [18].

Associations of Insulin with other chemical compounds

• Resveratrol, a SIRT1 activator, enhanced insulin sensitivity in vitro in a SIRT1-dependent manner and attenuated high-fat-diet-induced insulin resistance in vivo at a dose of 2.5 mg/kg/day [19].
• We provide evidence that ephrin-A5 is required for glucose-stimulated insulin secretion [20].
• Adiponectin-induced oxidants cause the oxidation/inhibition of protein-tyrosine phosphatase (PTP) 1B, one of the major phosphotyrosine phosphatases involved in the control of insulin receptor phosphorylation [21].
• Insulin-stimulated glucose uptake increased significantly in FEN (4.3 +/- 0.6 vs. 4.5 +/- 0.7 PLA and 5.2 +/- 0.5 vs. 7.6 +/- 0.6 mg/kg per minute FEN; pretreatment vs. posttreatment; P = 0.003) [22].
• Tacrolimus-induced diabetes in the rat seems to be mainly provoked by a decreased insulin gene transcription with little or no alteration of islet mass [23].
• The aggregates were finally matured in the presence of insulin-like growth factor II and nicotinamide [24].
• We also show that oleic acid treatment decreases the insulin sensitivity of heart muscle cells, and this sensitivity is completely restored by transfection with SNAP23 [25].
• EGF also increased plasma insulin levels and mediated glucose lowering in normal and diabetic mice [26].
• The metabolic activity in the first 2 h after injection was higher with ultra-fast insulin and insulin lispro than with human soluble insulin (AUC glucose infusion rate [GIR] 0-120 min: 915 +/- 301 and 781 +/- 174 vs 580 +/- 164 mg/kg; p < 0.05) [27].
• SHC-1 acts upstream of the insulin/IGF receptor DAF-2 and the PI3 kinase AGE-1 and directly interacts with DAF-2 [28].
• The EGL-4 cGMP-dependent protein kinase functions downstream of insulin and TGF-beta in sensory neurons including ASI to control quiescence in response to food intake [29].
• A standardized protocol of intravenous insulin before 18F-FDG injection in diabetic cancer patients was safe and effective in reducing glycemia [30].
• These combined results strongly suggest that insulin induces ROS generation trough NADPH activation and that this ROS increase is required for the intracellular Ca2+ rise mediated by inositol 1,4,5-trisphosphate receptors [31].
• The postintervention serum levels of osteocalcin were associated with both insulin sensitivity (r = 0.49; P = 0.03) and fasting triglycerides (r = -0.54; P = 0.01) [32].
• Induction of Myc by insulin is inhibited by the presence of the TOR inhibitor rapamycin, suggesting that insulin-induced Myc protein accumulation depends on the activation of TOR complex 1 [33].
• In association with increased hepatic mFAO capacity, liver CPT1mt expression improved glucose tolerance and insulin response to a glucose load in HF/HS and ob/ob mice, showing increased insulin sensitivity, and corrected IR in ob/ob mice [34].

Gene context of Insulin

• Ectopic expression of PTP-MEG2 in cells inhibited insulin-induced phosphorylation of the insulin receptor, while RNAi-mediated reduction of PTP-MEG2 transcript levels enhanced insulin action [35].
• These experiments establish a new role for Abca1 in beta-cell cholesterol homeostasis and insulin secretion, and suggest that cholesterol accumulation may contribute to beta-cell dysfunction in type 2 diabetes [36].
• Functional ablation of PKCepsilon selectively enhanced insulin release ex vivo from diabetic or lipid-pretreated islets and optimized the glucose-regulated lipid partitioning that amplifies the secretory response [37].
• We propose that ASNA1 is an evolutionarily conserved modulator of insulin signaling [38].
• It also reduces adipose mass, consequently attenuating insulin resistance and activation of JNK and IKKbeta, while improving insulin signalling in liver and muscle [39].
• We have now found that IGF-I can function through both splice variants of the IR, in spite of low affinity, to specifically activate IRS-2 to levels similar to those seen with equivalent concentrations of insulin or IGF-II [40].
• In the second model, we examined the relative significance of insulin versus IGF1 receptors in islet growth by feeding high-fat diets to beta IRKO and beta-cell-specific IGF1 receptor knockout (beta IGFRKO) mice [41].
• We conclude that genetic variation in the CACNA1E gene contributes to an increased risk of the development of type 2 diabetes by reducing insulin secretion [42].

• In the brains of ns3 mutants, excess serotonin and insulin accumulate, while peripheral insulin pathway activation is low [43].
• Insulin(+) cells were rarely noted in the pancreas transplant ducts in three SPK patients without islet autoimmunity and in six of 16 non-diabetic organ donors; these insulin(+) cells were never CK-19(+) [44].
• Overexpression of PC in INS-1 cells led to an elevation of insulin secretion and cell proliferation, whereas inhibition of PDH activity by overexpressing Pdk4 in INS-1 cells did not reduce insulin secretion [45].
• We conclude that unlike regular insulin and other insulin analogs, Lantus strongly activates the IGF-IR and the MAP kinase pathway in MCF7 cells and is a strong mitogen for cells characterized by a high-IGF-IR/IR ratio [46].

References