Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The epidemic of type 2 diabetes and impaired glucose tolerance is one of the main causes of morbidity and mortality worldwide. In both disorders, tissues such as muscle, fat and liver become less responsive or resistant to insulin. This state is also linked to other common health problems, such as obesity, polycystic ovarian disease, hyperlipidaemia, hypertension and atherosclerosis. The pathophysiology of insulin resistance involves a complex network of signalling pathways, activated by the insulin receptor, which regulates intermediary metabolism and its organization in cells. But recent studies have shown that numerous other hormones and signalling events attenuate insulin action, and are important in type 2 diabetes.
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PMID:Insulin signalling and the regulation of glucose and lipid metabolism. 1174 12

Insulin resistance is a key pathophysiologic feature of obesity and type 2 diabetes and is associated with other human diseases, including atherosclerosis, hypertension, hyperlipidemia, and polycystic ovarian disease. Yet, the specific cellular defects that cause insulin resistance are not precisely known. Insulin receptor substrate (IRS) proteins are important signaling molecules that mediate insulin action in insulin-sensitive cells. Recently, serine phosphorylation of IRS proteins has been implicated in attenuating insulin signaling and is thought to be a potential mechanism for insulin resistance. However, in vivo increased serine phosphorylation of IRS proteins in insulin-resistant animal models has not been reported before. In the present study, we have confirmed previous findings in both JCR:LA-cp and Zucker fatty rats, two genetically unrelated insulin-resistant rodent models, that an enhanced serine kinase activity in liver is associated with insulin resistance. The enhanced serine kinase specifically phosphorylates the conserved Ser(789) residue in IRS-1, which is in a sequence motif separate from the ones for MAPK, c-Jun N-terminal kinase, glycogen-synthase kinase 3 (GSK-3), Akt, phosphatidylinositol 3'-kinase, or casein kinase. It is similar to the phosphorylation motif for AMP-activated protein kinase, but the serine kinase in the insulin-resistant animals was shown not to be an AMP-activated protein kinase, suggesting a potential novel serine kinase. Using a specific antibody against Ser(P)(789) peptide of IRS-1, we then demonstrated for the first time a striking increase of Ser(789)-phosphorylated IRS-1 in livers of insulin-resistant rodent models, indicating enhanced serine kinase activity in vivo. Taken together, these data strongly suggest that unknown serine kinase activity and Ser(789) phosphorylation of IRS-1 may play an important role in attenuating insulin signaling in insulin-resistant animal models.
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PMID:In vivo phosphorylation of insulin receptor substrate 1 at serine 789 by a novel serine kinase in insulin-resistant rodents. 1200 86

In mammals, insulin signaling regulates glucose homeostasis and plays an essential role in metabolism, organ growth, development, fertility, and lifespan. The defects in this signaling pathway contribute to various metabolic diseases such as type 2 diabetes, polycystic ovarian disease, hypertension, hyperlipidemia, and atherosclerosis. However, reducing the insulin signaling pathway has been found to increase longevity and delay the aging-associated diseases in various animals, ranging from nematodes to mice. These seemly paradoxical findings raise an interesting question as to how modulation of the insulin signaling pathway could be an effective approach to improve metabolism and aging. In this review, we summarize current understanding on tissue-specific functions of insulin signaling in the regulation of metabolism and lifespan. We also discuss the potential benefits and limitations in modulating tissue-specific insulin signaling pathway to improve metabolism and healthspan.
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PMID:Tissue-specific insulin signaling in the regulation of metabolism and aging. 2508 68

Obesity is one of the leading causes of morbidity and mortality worldwide. Obese women are at increased risk of developing Type 2 Diabetes, cardiovascular diseases, hyperlipidemia, rectal carcinoma and gynecological problems including sub fertility, menstrual dysfunction and polycystic ovarian disease. The aim of this study was to assess relationship of obesity with menstrual irregularity in young girls that can help to create awareness among young girls about obesity and how it can affect fertility. It was a case controlled cross sectional study comprising of 220 participants from different colleges and universities of Karachi and from outpatients department of private clinic and Civil Hospital Karachi. A questionnaire was designed to assess the relationship of obesity with irregular menstrual cycle. Questionnaires were filled by co-authors after taking verbal consent. Data was collected from March 2013 to December 2013 and entered and analyzed on SPSS 16.0. Out of 220 participants obese and overweight were 67(30.4%) and 49(22.2%) respectively. Significant association was found between body composition and menstrual cycle irregularity as menstrual irregularity was present in only 9.5% when the BMI was normal and 14.09% and 24% girls in the overweight and obese categories respectively. Waist to hip ratio was found increased in 61.36% of girls. Sixty four point forty four percent (64.44%) of the girls with increased waist to hip ratio reported menstrual irregularity which makes 39.55% of the total sample population. Dysmenorrhea was reported by 63.6% of participants and family history was positive in 77.3%. Hirsutism was reported in 36.7% and 49.2%, acne in 34.6% and 43.2%, weight gain tendency in 85.7% and 98.5%, types 2 diabetes in 0% and 4.4% and hypertension in 8.16% and 31.3% of overweight and obese participants respectively. This study shows considerable association between overall and central obesity with menstrual cycle irregularity. This study provides the grounds on which foundation of health promotion and awareness programs can be laid for targeted age group.
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PMID:Obesity with irregular menstrual cycle in young girls. 2572 83

Gynostrmma pentaphyllum seed oil (GPSO), extracted from G. pentaphyllum seeds, is rich in conjugated linolenic acid, which is a special fatty acid consisting of cis-9, trans-11, trans-13 isomers. Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia resulting from insulin resistance, and is usually accompanied by hypertension, hyperlipidemia, atherosclerosis (i.e., the metabolic syndrome, or syndrome X), and polycystic ovarian disease. This study aimed to investigate the effect of GPSO on T2DM hepatic lipid metabolism and the underlying mechanism involving level of protein expression. In the experiment, the model of T2DM was established. Kunming male mice were fed with a high-fat diet and injected with streptozocin, in which the exploration of detailed mechanism in the therapy of T2DM was targeted. The results showed that the ability of oral glucose tolerance was improved in the GPSO group. Biochemical indices also revealed that GPSO had a positive effect on hypoglycemic activity, suggesting that GPSO could promote the expression of glucose transporter 4 in liver and skeletal muscle.
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PMID:Conjugated fatty acid-rich oil from Gynostrmma pentaphyllum seed can ameliorate lipid and glucose metabolism in type 2 diabetes mellitus mice. 2894 7