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Proceedings of the Japan Academy.... 2019Immunoprecipitation with autoantibodies to the insulin receptor derived from patients with extreme insulin resistance and acanthosis nigricans revealed that the receptor... (Review)
Review
Immunoprecipitation with autoantibodies to the insulin receptor derived from patients with extreme insulin resistance and acanthosis nigricans revealed that the receptor is comprised of two subunits of 135 kDa (α subunit) and 95 kDa (β subunit) and that insulin induces the rapid phosphorylation of the β subunit in intact cells. Incubation of a highly purified insulin receptor preparation with [γ-P]ATP also resulted in tyrosine phosphorylation of the β subunit in an insulin-dependent manner, suggesting that the receptor itself is a tyrosine-specific protein kinase. Furthermore, a Japanese boy with insulin resistance and acanthosis nigricans was found to be heterozygous for a mutation of the insulin receptor gene that resulted in the replacement of glycine-996 with valine in the ATP binding site of the receptor. Expression of the mutant receptor in cultured cells revealed it to be deficient in tyrosine kinase activity and mediation of insulin action, suggesting that the tyrosine kinase activity of the insulin receptor is essential for insulin action in vivo.
Topics: Adenosine Triphosphate; Amino Acid Sequence; Animals; Binding Sites; Humans; Insulin; Insulin Resistance; Mutation; Phosphorylation; Protein Binding; Protein-Tyrosine Kinases; Receptor, Insulin; Tyrosine
PubMed: 31827016
DOI: 10.2183/pjab.95.039 -
TheScientificWorldJournal 2015In medical practice, almost every clinician may encounter patients with skin disease. However, it is not always easy for physicians of all specialties to face the daily... (Meta-Analysis)
Meta-Analysis Review
In medical practice, almost every clinician may encounter patients with skin disease. However, it is not always easy for physicians of all specialties to face the daily task of determining the nature and clinical implication of dermatologic manifestations. Are they confined to the skin, representing a pure dermatologic event? Or are they also markers of internal conditions relating to the patient's overall health? In this review, we will discuss the principal cutaneous conditions which have been linked to metabolic alterations. Particularly, since insulin has an important role in homeostasis and physiology of the skin, we will focus on the relationships between insulin resistance (IR) and skin diseases, analyzing strongly IR-associated conditions such as acanthosis nigricans, acne, and psoriasis, without neglecting emerging and potential scenarios as the ones represented by hidradenitis suppurativa, androgenetic alopecia, and hirsutism.
Topics: Humans; Hyperandrogenism; Hyperinsulinism; Insulin; Insulin Resistance; Signal Transduction; Skin Diseases
PubMed: 25977937
DOI: 10.1155/2015/479354 -
Indian Journal of Dermatology and... 1966
PubMed: 29176258
DOI: No ID Found -
Cureus Apr 2023Background Polycystic ovarian syndrome (PCOS), which affects women of reproductive age, is the most prevalent endocrine disorder. Signs of excessive androgen, irregular...
Background Polycystic ovarian syndrome (PCOS), which affects women of reproductive age, is the most prevalent endocrine disorder. Signs of excessive androgen, irregular menses, prolonged anovulation, and infertility are characteristics of the clinical phenotype. Women with PCOS are more likely to have diabetes, obesity, dyslipidemia, hypertension, anxiety, and depression. PCOS affects women's health starting before conception and continuing through their post-menopausal years. Methods Ninety-six study subjects were recruited from women visiting the gynaecology clinic according to the Rotterdam criteria for PCOS. Study subjects were then divided into lean and obese groups according to their body mass index (BMI). Demographic data, and obstetrical and gynaecological history were obtained including marital status, menstrual cycle regularity, recent abnormal weight gain (in the preceding six months), and subfertility. To identify any clinical signs of hyperandrogenism such as acne, acanthosis nigricans, or hirsutism, a general and systemic examination was conducted. Data were analyzed after the clinico-metabolic profile was assessed, compared, and contrasted between the two groups. Results The findings showed a significant correlation between obese women with PCOS and the clinical profile of PCOS i.e. menstrual irregularities, acne vulgaris, acanthosis nigricans and hirsutism; the waist-hip ratio was higher in both groups. Higher levels of fasting insulin, fasting glucose: insulin ratio, postprandial sugars, homeostasis model assessment of insulin resistance (HOMA-IR) index, total testosterone, free testosterone, and luteinizing hormone/follicle-stimulating hormone (LH: FSH) ratio were seen in obese women with PCOS, whereas the levels of fasting glucose, serum triglycerides, serum high-density lipoprotein cholesterol (HDL) were higher in all the study subjects irrespective of BMI. Conclusion The study showed that women with PCOS have a deranged metabolic profile like abnormal blood sugar, insulin resistance (IR), and hyperandrogenemia with clinical derangements like irregular menses, subfertility, and recent weight gain more frequently with higher BMI.
PubMed: 37214034
DOI: 10.7759/cureus.37809 -
World Journal of Diabetes May 2021Insulin has complex effects on cell growth, metabolism and differentiation, and these effects are mediated by a cell-surface bound receptor and eventually a cascade of... (Review)
Review
Insulin has complex effects on cell growth, metabolism and differentiation, and these effects are mediated by a cell-surface bound receptor and eventually a cascade of intracellular signaling events. Among the several metabolic and growth-promoting effects of insulin, insulin resistance is defined as an attenuated effect of insulin on glucose metabolism, primarily the limited export of blood glucose into skeletal muscle and adipose tissue. On the other hand, not all the signaling pathways and insulin-responsive tissues are equally affected, and some effects other than the metabolic actions of insulin are overexpressed. Ovaries and the adrenal glands are two examples of tissues remaining sensitive to insulin actions where insulin may contribute to increased androgen secretion. Polycystic ovary syndrome (PCOS) is the most common form of androgen excess disorder (AED), and its pathogenesis is closely associated with insulin resistance. Patients with idiopathic hirsutism also exhibit insulin resistance, albeit lower than patients with PCOS. Although it is not as evident as in PCOS, patients with congenital adrenal hyperplasia may have insulin resistance, which may be further exacerbated with glucocorticoid overtreatment and obesity. Among patients with severe insulin resistance syndromes, irrespective of the type of disease, hyperinsulinemia promotes ovarian androgen synthesis independently of gonadotropins. It is highly debated in whom and how insulin resistance should be diagnosed and treated among patients with AEDs, including PCOS. It is not suitable to administer an insulin sensitizer relying on only some mathematical models used for estimating insulin resistance. Instead, the treatment decision should be based on the constellation of the signs, symptoms and presence of obesity; acanthosis nigricans; and some laboratory abnormalities such as impaired glucose tolerance and impaired fasting glucose.
PubMed: 33995849
DOI: 10.4239/wjd.v12.i5.616 -
Indian Dermatology Online Journal 2019The American Diabetes Association includes acanthosis nigricans (AN) as an indicator of diabetes mellitus risk in overweight youth entering puberty. Some argue that AN...
INTRODUCTION
The American Diabetes Association includes acanthosis nigricans (AN) as an indicator of diabetes mellitus risk in overweight youth entering puberty. Some argue that AN is not an independent predictor of insulin resistance (IR), when body mass index (BMI) is controlled for. There is a paucity of studies on the association of AN and IR among children and young adults from India. Homeostatic model assessment-IR (HOMA2-IR), a computerized updated model, which is supposed to be superior to HOMA1-IR, has rarely been used for quantification of IR.
METHODS
Sixty cases (irrespective of BMI), aged 2-24 years with AN, and 30 age- and sex-matched normal weight controls were included. A thorough clinical examination and grading of AN was done. BMI, fasting glucose levels, and fasting insulin levels were measured for all. HOMA-IR calculator V.2.2.3 was used to calculate IR. Those with HOMA 2-IR >1.8 were considered insulin-resistant. Lifestyle modifications were advised for patients with IR.
RESULTS
The mean HOMA2-IR value in cases and controls was 2.422 and 1.322, respectively, which was statistically significant. Overweight and obese cases had 2.5 and 11.25 times higher risk of having IR, respectively, by logistic regression. The association of AN with IR was found to be statistically significant in normal weight cases when compared with controls ( = 0.045). Grade 4 of neck severity ( = 0.007), Grade 3 of neck texture ( = 0.001), and Grade 4 of axillary severity ( = 0.001) of AN were found to be significantly associated with IR.
LIMITATIONS
The relatively small sample size may not reflect the accuracy of AN as a marker of IR.
CONCLUSION
Acanthosis nigricans is associated with IR in both normal and obese. We propose that all children, adolescents, and youth with AN be screened for IR irrespective of BMI. Early identification and prompt lifestyle interventions may prevent or delay the onset of diabetes later.
PubMed: 31149570
DOI: 10.4103/idoj.IDOJ_303_18 -
Indian Journal of Dermatology,... 2013Acquired pigmentary disorders are group of heterogenous entities that share single, most significant, clinical feature, that is, dyspigmentation. Asians and Indians, in... (Review)
Review
Acquired pigmentary disorders are group of heterogenous entities that share single, most significant, clinical feature, that is, dyspigmentation. Asians and Indians, in particular, are mostly affected. Although the classic morphologies and common treatment options of these conditions have been reviewed in the global dermatology literature, the value of histpathological evaluation has not been thoroughly explored. The importance of accurate diagnosis is emphasized here as the underlying diseases have varying etiologies that need to be addressed in order to effectively treat the dyspigmentation. In this review, we describe and discuss the utility of histology in the diagnostic work of hyperpigmentary disorders, and how, in many cases, it can lead to targeted and more effective therapy. We focus on the most common acquired pigmentary disorders seen in Indian patients as well as a few uncommon diseases with distinctive histological traits. Facial melanoses, including mimickers of melasma, are thoroughly explored. These diseases include lichen planus pigmentosus, discoid lupus erythematosus, drug-induced melanoses, hyperpigmentation due to exogenous substances, acanthosis nigricans, and macular amyloidosis.
Topics: Dermatology; Humans; Hyperpigmentation; Melanosis; Pathology, Clinical
PubMed: 23619441
DOI: 10.4103/0378-6323.110798 -
Anais Brasileiros de Dermatologia 2013The skin often signals systemic changes. Some neoplastic diseases that affect internal organs may trigger several cutaneous manifestations. Although these dermatoses are... (Review)
Review
The skin often signals systemic changes. Some neoplastic diseases that affect internal organs may trigger several cutaneous manifestations. Although these dermatoses are relatively unusual, the recognition of some typical paraneoplastic dermatoses may lead to the early diagnosis of a neoplasm and determine a better prognosis. In this review article, we discuss the paraneoplastic cutaneous manifestations strongly associated with neoplasms, which include acanthosis nigricans maligna, tripe palms, erythema gyratum repens, Bazex syndrome, acquired hypertrichosis lanuginosa, necrolytic migratory erythema, Leser-Trélat sign and paraneoplastic pemphigus. We also review the clinical manifestations of each condition and include updated knowledge on disease pathogenesis.
Topics: Education, Medical, Continuing; Humans; Necrosis; Paraneoplastic Syndromes; Prognosis; Skin Diseases; Surveys and Questionnaires
PubMed: 23538999
DOI: 10.1590/s0365-05962013000100001 -
Indian Journal of Dermatology Nov 2011Acanthosis nigricans (AN) is a dermatosis characterized by thickened, hyperpigmented plaques, typically on the intertriginous surfaces and neck. Common in some...
BACKGROUND
Acanthosis nigricans (AN) is a dermatosis characterized by thickened, hyperpigmented plaques, typically on the intertriginous surfaces and neck. Common in some populations, its prevalence depends on race. Clinicians should recognize AN; it heralds disorders ranging from endocrinologic disturbances to malignancy. In this review, we discuss the pathogenesis of AN and its clinical implications and management.
MATERIALS AND METHODS
We selected 30 patients for the study. Diagnosis of associated disorders was established by history, physical examination, body mass index (BMI), hormone measurements by radioimmunoassays of thyroidnfunction tests, free testosterone, 17 (OH) progesterone, dehydroepiandrosterone sulfate (DHEAS), cortisol, gonadotropins, prolactin, immunoreactive insulin, and C-peptide levels.
RESULTS AND DISCUSSION
In our study, the flexural involvement (flexures of groins, knees and elbows) was seen in 40% patients, lip involvement was seen in 6.6% patients, and dorsal involvement was seen in 3.3% patients each. Increased serum testosterone levels were seen in 13.3% patients and increased DHEAS levels were seen in 20% patients. Regarding the types of AN, obesity induced AN or pseudo-AN was seen 70% patients, syndromic AN was seen in 23.35% patients and malignant AN was seen in 6.6% patients. The commonest histopathological feature of patients with AN was hyperkeratosis, seen in 100% patients, papillomatosis was seen in 90% patients, dermal infiltrate of lymphocytes and plasma cells was seen in 60% patients, horn pseudocysts were seen in 30% patients, and irregular acanthosis was seen in 26.6% patients.
PubMed: 22345770
DOI: 10.4103/0019-5154.91828 -
International Journal of Women's... Jun 2021Hirsutism is common across ethnicities and a significant cause of negative self-esteem from presumptive loss of femininity. It remains understudied in Indian patients. (Review)
Review
BACKGROUND
Hirsutism is common across ethnicities and a significant cause of negative self-esteem from presumptive loss of femininity. It remains understudied in Indian patients.
OBJECTIVE
We studied the clinical and investigative attributes of patients with hirsutism.
METHODS
The medical records of 233 patients with hirsutism diagnosed between 2014 and 2019 were analyzed retrospectively.
RESULTS
The complete records of 122 patients age 14 to 45 years were available. Approximately 32% were adolescents, and 50% patients were age 21 to 30 years. The mean ± standard deviation modified Ferriman-Gallway (mF-G) score was 17.95 ± 10.58, and hirsutism was graded zero/mild in 57.4% patients. Polycystic ovaries were present in 29.5% of patients. Serum-free testosterone levels were elevated in 16.4% of patients. Associated signs of clinical hyperandrogenism, such as acne, obesity, acanthosis nigricans, and menstrual irregularities, were present in 12 patients (9.8%). Familial hirsutism occurred in 13% of patients and was idiopathic in 10.7% of patients. Significantly more patients (47.7% vs. 27.9%) with severe hirsutism did not complete investigations compared with those with mild hirsutism (45.9% vs. 21.6%), which may be due to the high cost of investigative work-up (as often stated by many patients) compared with periodic depilation.
LIMITATIONS
The mF-G score is a visual and subjective scale, and its validity remains limited by interobserver variations. The score's cut-off values may vary among races/ethnicities. A small number of patients and the retrospective study design are other limitations.
CONCLUSION
Hirsutism of polycystic ovary syndrome or idiopathic origin is not uncommon in Indian women. Hirsutism of adrenal or thyroid origin remains uncommon. Self-referral and high cosmetic concerns for facial hair were common in adolescents and young unmarried patients, and the majority had an mF-G score of < 8 to 16. Cut-off values for the mF-G score specific to our population assigning higher than current mF-G value to facial hair are highly desirable.
PubMed: 34222577
DOI: 10.1016/j.ijwd.2020.11.007