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Peripubertal hyperinsulinemia upregulates phosphatidylinositol 3-kinase/akt pathway in rat ovaries.

OBJECTIVE: Polycystic ovary syndrome (PCOS) usually develops during peripuberty and is often associated with hyperinsulinemia. Paradoxically, hyperinsulinemic patients with PCOS develop peripheral insulin resistance but retain ovarian insulin sensitivity. We investigated the effect of peripubertal hyperinsulinemia on insulin signaling pathways in rat ovaries. METHODS: Hyperinsulinemia was induced in peripubertal female rats by infusing insulin (0.14 IU/day) for 4 weeks. Control animals received normal saline. At autopsy, trunk blood was collected for insulin assay; ovaries were collected for

Whole body glucoregulation and tissue-specific glucose uptake in a novel Akt substrate of 160 kDa knockout rat model.

Akt substrate of 160 kDa (also called AS160 or TBC1D4) is a Rab GTPase activating protein and key regulator of insulin-stimulated glucose uptake which is expressed by multiple tissues, including skeletal muscle, white adipose tissue (WAT) and the heart. This study introduces a novel rat AS160-knockout (AS160-KO) model that was created using CRISPR/Cas9 technology. We compared male AS160-KO versus wildtype (WT) rats for numerous metabolism-related endpoints. Body mass, body composition, energy expenditure and physical activity did not differ between genotypes. Oral glucose intolerance was detec

Fructose only in pregnancy provokes hyperinsulinemia, hypoadiponectinemia, and impaired insulin signaling in adult male, but not female, progeny.

PURPOSE: Fructose intake from added sugars correlates with the epidemic rise in metabolic syndrome and cardiovascular diseases. However, consumption of beverages containing fructose is allowed during gestation. Recently, we found that an intake of fructose (10 % wt/vol) throughout gestation produces impaired fetal leptin signaling and hepatic steatosis. Therefore, we have investigated whether fructose intake during pregnancy produces subsequent changes in the progeny, when adult. METHODS: Fed 261-day-old male and female descendants from fructose-fed, control or glucose-fed mothers were used.

A randomised trial examining inflammatory signaling in acutely induced hyperinsulinemia and hyperlipidemia in normal weight women-the reprometabolic syndrome.

CONTEXT: Obesity, is a state of chronic inflammation, characterized by elevated lipids, insulin resistance and relative hypogonadotropic hypogonadism. We have defined the accompanying decreased Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH), ovarian steroids and reduced pituitary response to Gonadotropin-releasing Hormone (GnRH) as Reprometabolic syndrome, a phenotype that can be induced in healthy normal weight women (NWW) by acute infusion of free fatty acids and insulin. OBJECTIVE: To identify potential mediators of insulin and lipid-related reproductive endocrine dysfunction

MDG-1, a polysaccharide from Ophiopogon japonicus exerts hypoglycemic effects through the PI3K/Akt pathway in a diabetic KKAy mouse model.

ETHNOPHARMACOLOGICAL RELEVANCE: Ophiopogon japonicus is a traditional Chinese medicine that might be helpful for the treatment of type 2 diabetes. Recent studies have confirmed its beneficial properties, but not the mechanism of action. AIM OF STUDY: In this study, we examined the effects of a water-soluble β-d-fructan (MDG-1) from O. japonicus on type 2 diabetes through the PI3K/Akt pathway in a diabetic KKAy mouse model. MATERIALS AND METHODS: MDG-1 was extracted from the tube root of O. japonicus and purified as described previously (Xu et al., 2005). The KKAy mice were gavaged once daily

[Blood pressure and heart rate regulation in diabetics].

Cardiac autonomic neuropathy (CAN) is frequent in subclinical stages. Its prognostic value has been demonstrated. Cardiac autonomic neuropathy induces different functional cardiac changes, especially a reduction in left ventricular contractility and changes in ventricular repolarisation. It is also associated with changes in the daily variations in blood pressure. The association of CAN and silent myocardial ischaemia significantly worsens the prognosis. The investigation of CAN in the greatest number of diabetic patients is therefore justified. The study of heart rate variations during deep r

A Case Study of a Rare Disease (Fructosemia) Diagnosed in a Patient with Abdominal Pain.

Hereditary fructose intolerance is a rare genetic disorder that is inherited in an autosomal recessive manner, with mutations sometimes occurring spontaneously. Consuming fructose triggers biochemical abnormalities, disrupting liver processes like glycogenolysis and gluconeogenesis. Recent studies have revealed elevated intrahepatic fat levels in affected individuals. Symptoms include aversion to fructose-containing foods, hypoglycemia, liver and kidney dysfunction, and growth delays, with severe cases leading to liver enlargement, fatty liver disease, kidney failure, and life-threatening hypo

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… Such symptoms may occur as a result of hormonal disorders such as congenital hyperinsulinism (channel disorders, metabolic disorders, transcription-factor disorders, syndromic disorders, congenital disorders of glycosylation), adrenal insufficiency, congenital pituitary insufficiency and growth hormone …

AMPK activation prevents excess nutrient-induced hepatic lipid accumulation by inhibiting mTORC1 signaling and endoplasmic reticulum stress response.

Lipid accumulation is a central event in the development of chronic metabolic diseases, including obesity and type 2 diabetes, but the mechanisms responsible for lipid accumulation are incompletely understood. This study was designed to investigate the mechanisms for excess nutrient-induced lipid accumulation and whether activation of AMP-activated protein kinase (AMPK) prevents the hepatic lipid accumulation in excess nutrient-treated HepG2 cells and high fat diet (HFD)-fed mice. Exposure of HepG2 cells to high levels of glucose or palmitate induced the endoplasmic reticulum (ER) stress respo

Antibodies to watch in 2026.

The Antibodies to Watch article series provides annual updates on commercial late-stage clinical development, regulatory review, and marketing approvals of antibody therapeutics. Since the first article was published in 2010, the late-stage pipeline has grown from 26 antibody therapeutics to over 200, while during the same time numerous molecules in late-stage studies either transitioned to regulatory review and were approved or were terminated. In this installment of the series, we recap first marketing approvals granted to 19 antibody therapeutics in 2025, discuss 26 molecules currently in r

Toward fully exploiting the therapeutic potential of marketed pharmaceuticals: the use of octreotide and chloroquine in oncology.

Pleiotropy in biological systems and their targeting allows many pharmaceuticals to be used for multiple therapeutic purposes. Fully exploiting the therapeutic properties of drugs that are already marketed would be highly advantageous. This is especially the case in the field of oncology, where the ineffectiveness of typical anticancer agents is a common issue, while the development of novel anticancer agents is a costly and particularly time-consuming process. Octreotide and chloroquine are two pharmaceuticals that exhibit profound antitumorigenic activities. However, the current therapeutic

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… 5491.2009.02766.x 29 Bello SO Rahamim J High-dose intravenous octreotide is safe and may be superior to surgery in managing severe postesophagectomy chylothorax in high-risk patients Ann Thorac Surg 2015 100 1 297 299 26140770 10.1016/j.athoracsur.2014.08.058 30 Arnoux JB Verkarre V Saint-Martin C Congenital hyperinsulinism … : current trends in diagnosis and therapy Orphanet J Rare Dis 2011 6 1 63 21967988 10.1186/1750-1172-6-63 PMC3199232 31 Hosokawa Y Kawakita R Yokoya S Efficacy and safety of octreotide for the treatment of congenital hyperinsulinism: a prospective, open-label clinical trial and an observational study …

Discovery of Novel Lipid Profiles in PCOS: Do Insulin and Androgen Oppositely Regulate Bioactive Lipid Production?

CONTEXT: Polycystic ovary syndrome (PCOS) is a complex syndrome showing clinical features of an endocrine/metabolic disorder, including hyperinsulinemia and hyperandrogenism. Polyunsaturated fatty acids (PUFAs) and their derivatives, both tightly linked to PCOS and obesity, play important roles in inflammation and reproduction. OBJECTIVE: This study aimed to investigate serum lipid profiles in newly diagnosed patients with PCOS using lipidomics and correlate these features with the hyperinsulinemia and hyperandrogenism associated with PCOS and obesity. DESIGN AND SETTING: Thirty-two newly di

Innovative Peptide Therapeutics in the Pipeline: Transforming Cancer Detection and Treatment.

Cancer remains a leading global health burden, profoundly affecting patient survival and quality of life. Current treatments-including chemotherapy, radiotherapy, immunotherapy, and surgery-are often limited by toxicity or insufficient specificity. Conventional chemotherapy, for instance, indiscriminately attacks rapidly dividing cells, causing severe side effects. In contrast, peptide-based therapeutics offer a paradigm shift, combining high tumour-targeting precision with minimal off-target effects. Their low immunogenicity, multi-pathway modulation capabilities, and adaptability for diagnos

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… Similarly, the SST2-selective agonist CRN02481 effectively controls pathological insulin secretion in hyperinsulinism, proving that targeted SSTR modulation can regulate aberrant endocrine signalling [ 101 ]. … A selective nonpeptide somatostatin receptor 5 agonist effectively decreases insulin secretion in hyperinsulinism. J. Biol. Chem. 2023;299:104816. doi: 10.1016/j.jbc.2023.104816. 102. Rogoza O., Megnis K., Kudrjavceva M., Gerina-Berzina A., Rovite V. …

Glucose intolerance and resistin expression in rat offspring exposed to ethanol in utero: modulation by postnatal high-fat diet.

High-fat diet and intrauterine growth retardation may predispose to obesity, insulin resistance, and type 2 diabetes. Because prenatal ethanol (ETOH) exposure causes intrauterine growth retardation, we investigated its interactions with postnatal high-fat diet on glucose tolerance and adipocyte-derived hormones in the rat offspring. High-fat-fed offspring had increased adiposity, serum leptin, and muscle uncoupling protein-3, but decreased adiponectin mRNA, compared with corresponding chow-fed groups. ETOH-exposed offspring had normal adiponectin, but increased resistin mRNA and protein, compa

Adaptive changes in insulin secretion by islets from neonatal rats raised on a high-carbohydrate formula.

Artificial rearing of neonatal rats on a high-carbohydrate (HC) milk formula resulted in the immediate onset of hyperinsulinemia. This study examines, in islets of 12-day-old HC rats, adaptive changes that support the hyperinsulinemic state. Increases in plasma glucagon-like peptide-1 (GLP-1) levels and islet GLP-1 receptor mRNA supported increased insulin secretion by HC islets. Isolated HC islets, but not mother-fed (MF) islets, secreted moderate amounts of insulin in a glucose- and Ca(2+)-independent manner. Under stringent Ca(2+)-free conditions and in the presence of glucose, GLP-1 plus a

[Polycystic ovary syndrome of extra-ovarian origin. Review].

An established fact in the polycystic ovarian syndrome (POS) is an abnormal ovarian steroidogenesis. Though this suggest an intrinsic ovarian defect, the syndrome could also be influenced by factors outside the ovaries. Although of unknown etiology, the POS is one of the most frequent endocrine disorders in the gynecologic practice. The disorder is characterized by ultrasound findings of enlarged polycystic ovaries, hyperandrogenism, menstrual disorders, obesity and including the appearance of infertility. There are a series of mechanisms involved in the extraovarian androgen increase in patie

Модель индекса питания для прогнозирования резистентности и прогнозирования в множественных миеломах после аутологической трансплантации стволовых клеток.

Множественная миелома - это one Наиболее распространенные гематологические заболевания во всем мире создают серьезную угрозу для жизни и здоровья населения. В последние годы все больше и больше исследователей включили прогнозный индекс питания (ПНИ) в прогнозные исследования опухолей и провели оценку состояния питания и прогнозировали долгосрочный прогноз пациентов в рамках ПНИ. МЕТОДЫ: Медицинские записи 245 Пациенты с множественными миеломами, получившие автологическую трансплантацию стволовых клеток в нашей больнице с февраля 2011 по июль 2018 был ретроспективно проанализирован. Оптимальное

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… Although the exact mechanism by which DM affects cancer is not clear, it is generally accepted that hyperinsulinism leads to an increase in circulating levels of insulin-like growth factor-1 (IGF-1), which activates the mTOR signaling pathway and thus promotes tumour cell proliferation [ 30 ]. …

Endocrine paraneoplastic syndromes in lung cancer: A call for clinical vigilance (Review).

Endocrine paraneoplastic syndromes (PNS) are uncommon but clinically impactful manifestations associated with malignancies, particularly lung cancer, most notably small-cell lung cancer. These syndromes arise from ectopic hormone production by malignant cells, causing systemic effects that are independent of direct tumor invasion or metastasis. Their presentation often precedes or signals recurrence of the primary cancer, underscoring the importance of early recognition and targeted intervention. Common endocrine PNS in lung cancer include syndrome of inappropriate antidiuretic hormone secreti

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… Diagnosing hypoglycemia in non-diabetic patients requires evaluating medication effects, severe illness, organ dysfunction and hormone deficiencies while also differentiating endogenous hyperinsulinism. If a tumor is suspected, NITCH should be considered. …

[Genetics of type II diabetes].

Type 2 diabetes is a multifactorial disease composed of subtypes strongly associated with environmental factors at one end of the spectrum and highly genetic forms at the other hand. The former forms have been largely elucidated in the last years by the identification of the 5 genes responsible for the autosomal dominant MODY subtype: glucokinase, and 4 transcription factors which play a key role in the development of the endocrine pancreas or in the expression of glucose metabolism genes. Apart from the monogenic forms of type 2 diabetes little is known about the nature of the genetic factors

Emerging Role of GLP-1 Agonists in Obesity: A Comprehensive Review of Randomised Controlled Trials.

Obesity is a chronic disease with high prevalence and associated comorbidities, making it a growing global concern. These comorbidities include type 2 diabetes, hypertension, ventilatory dysfunction, arthrosis, venous and lymphatic circulation diseases, depression, and others, which have a negative impact on health and increase morbidity and mortality. GLP-1 agonists, used to treat type 2 diabetes, have been shown to be effective in promoting weight loss in preclinical and clinical studies. This review summarizes numerous studies conducted on the main drugs in the GLP-1 agonists class, outlini

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… Additionally, obesity is associated with osteoarticular complications such as arthrosis [ 9 ], venous and lymphatic circulatory disorders [ 25 ], endocrine complications including hyperinsulinism, hypercorticism, hypothyroidism, and hypogonadism [ 26 , 27 ], and oncological conditions such as endometrial …