Background and Objectives: Insulinoma is a rare tumor of the Langerhans islets of the pancreas. It produces insulin and causes severe hypoglycemia with neuroglycopenic symptoms. The incidence is low, at about 1-2 per 1 million inhabitants per year. The diagnosis is based on the presence of Whipple's triad and the result of a fasting test. Surgery is the treatment of choice. Objectives: A retrospective observational study of patients operated on for insulinoma in our hospital focused on the diagnosis, the type of surgery, and complications. Materials and Methods: We retrospectively reviewed patients operated on due to insulinoma. There were 116 surgeries between 2000 and 2022. There were 79 females and 37 males in this group. A fasting test and a CT examination were performed on all the patients. Results: The average duration of the fasting test was 18 h. Insulinoma was found in the body and tail of the pancreas in more than half of the patients. Enucleation was the most frequent type of surgery. Complications that were Clavien Dindo grade III or more occurred in 18% of the patients. The most frequent complications were abscesses and pancreatic fistula. Five patients had malignant insulinoma. Conclusions: Surgery is the treatment of choice in the case of insulinomas. The enucleation of the tumor is a sufficient treatment for benign insulinomas, which are not in contact with the main pancreatic duct. Due to the low incidence of the condition, the centralization of patients is recommended.

• Klíčová slova
• Whipple’s triad, hypoglycemia, insulinoma, pancreas,
• MeSH
• hypoglykemie * etiologie   MeSH
• inzulinom * diagnóza   chirurgie   MeSH
• lidé MeSH
• nádory slinivky břišní * diagnóza   chirurgie   MeSH
• pankreas MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

Hypoglycemia is a rather frequent complication of diabetes treatment, however it can occur also in non-diabetic patients. The article presents a brief differential diagnosis of hypoglycemia in non-diabetic patients.

• Klíčová slova
• hypoglycemia, insulinoma, postprandial hypoglycemia, type 2 diabetes,
• MeSH
• diabetes mellitus 2. typu * MeSH
• diferenciální diagnóza MeSH
• hypoglykemie * chemicky indukované   diagnóza   MeSH
• inzulinom * diagnóza   MeSH
• lidé MeSH
• nádory slinivky břišní * diagnóza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Regulation of cellular iron homeostasis is crucial as both iron excess and deficiency cause hematological and neurodegenerative diseases. Here we show that mice lacking iron-regulatory protein 2 (Irp2), a regulator of cellular iron homeostasis, develop diabetes. Irp2 post-transcriptionally regulates the iron-uptake protein transferrin receptor 1 (TfR1) and the iron-storage protein ferritin, and dysregulation of these proteins due to Irp2 loss causes functional iron deficiency in β cells. This impairs Fe-S cluster biosynthesis, reducing the function of Cdkal1, an Fe-S cluster enzyme that catalyzes methylthiolation of t6A37 in tRNALysUUU to ms2t6A37. As a consequence, lysine codons in proinsulin are misread and proinsulin processing is impaired, reducing insulin content and secretion. Iron normalizes ms2t6A37 and proinsulin lysine incorporation, restoring insulin content and secretion in Irp2-/- β cells. These studies reveal a previously unidentified link between insulin processing and cellular iron deficiency that may have relevance to type 2 diabetes in humans.

• MeSH
• beta-buňky metabolismus   MeSH
• homeostáza MeSH
• inzulin metabolismus   MeSH
• inzulinom genetika   metabolismus   MeSH
• krysa rodu Rattus MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• nádorové buněčné linie MeSH
• nádory slinivky břišní genetika   metabolismus   MeSH
• porucha glukózové tolerance genetika   MeSH
• proinsulin genetika   metabolismus   MeSH
• proteiny obsahující železo a síru metabolismus   MeSH
• regulační protein železa 2 genetika   metabolismus   MeSH
• RNA transferová Lys genetika   metabolismus   MeSH
• signální dráha UPR genetika   MeSH
• tRNA-methyltransferasy genetika   metabolismus   MeSH
• železo metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• CDKAL1 protein, mouse MeSH Prohlížeč
• inzulin MeSH
• Ireb2 protein, mouse MeSH Prohlížeč
• proinsulin MeSH
• proteiny obsahující železo a síru MeSH
• regulační protein železa 2 MeSH
• RNA transferová Lys MeSH
• tRNA-methyltransferasy MeSH
• železo MeSH

Multiple Endocrine Neoplasia (MEN) is a condition in which several endocrine organs of an individual are affected by adenoma, hyperplasia and less often carcinoma, either simultaneously or at different stages of life. Two existing syndromes, MEN1 and MEN2 (2A, 2B), in literature is also mentioned MEN4, are associated also with other non-endocrine disorders. MEN1 (Wermer syndrome) affects the pituitary, parathyroid, and pancreatic area. 95 % of patients show very early manifestation of hyperparathyroidism, often before 40 years of age. Multiple adenomas gradually involve all four parathyroid glands. The first clinical sign of MEN1 includes recurrent nephrolithiasis. The second most frequent manifestation of MEN1 is pancreatic area (pancreas, stomach and duodenum), again multiple malignancies of varying degree which can metastasize. Most often gastrinomas and insulinomas are involved. Pituitary adenomas occur in about one third of MEN1 patients and tend to be larger and less responsive to treatment. Tumors appearing most often are prolactinomas, tumors producing growth hormone, or afunctional adenomas. The other endocrine tumors include carcinoids and adrenal lesions. In the last year we have registered four MEN1 syndrome patients in our center and one patient has been already followed since 2008. In four out of five patients, nephrolithiasis after 30 years of age was the first clinical symptom, but only one of theses cases resulted in MEN1 diagnosis. In all patients, the clinical symptoms intensified and the diagnosis was established between 36 and 40 years of age. A crutial factor is a cooperation with the urology examination of kidney stones formation in young individuals with nephrolithiasis in order to reveal the potential cases of MEN1 syndrome very early on. Consider the MEN1 genetic diagnostics if recurrent primary hyperparathyroidism or recurrent gastroduodenal ulcer disease appear in patients under 40 years of age.Key words: carcinoid - gastrinoma - hyperparathyroidism - insulinoma - MEN1 - multiple endocrine neoplasia - nefrolithiasis - neuroendocrine tumor - pancreatic area - pituitary gland.

• MeSH
• adenom diagnóza   etiologie   MeSH
• dospělí MeSH
• gastrinom diagnóza   etiologie   MeSH
• hyperparatyreóza diagnóza   etiologie   MeSH
• inzulinom diagnóza   etiologie   MeSH
• lidé MeSH
• mnohočetná endokrinní neoplazie typu 1 komplikace   diagnóza   MeSH
• nádory hypofýzy diagnóza   etiologie   MeSH
• nádory příštítného tělíska diagnóza   etiologie   MeSH
• nádory slinivky břišní diagnóza   etiologie   MeSH
• nefrolitiáza etiologie   MeSH
• peptický vřed etiologie   MeSH
• prolaktinom diagnóza   etiologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

UNLABELLED: Decrease of blood glucose levels below 3 mmol/l is in fully developed cases accompanied by neuroglycopenic symptoms that may even lead to altered state of consciousness. The treating physician frequently faces a complicated situation. This may be due to inappropriately administered drugs including cases motivated by self-harm intentions (insulin, insulin secretagogues), or alcohol abuse. Undernourished people, or those afflicted with a serious systemic infection, end-stage liver or kidney diseases or with a failing heart, belong to a risk group. Hypoglycemia typically accompanies hypocorticism (Addisons disease) or lack of glucagon. Endogenous hyperinsulinism caused by a hormonally active pancreatic cancer, that is, by a neuroendocrine tumour - insulinoma, is a possibility to be considered. A hidden cause of hypoglycemias may be a pancreatic-beta- cell dysfunction (nesidioblastosis, or non-insulin pancreatogenous hypoglycemia). A similar situation may arise following gastric bypass surgery. Hypoglycemia incited by the presence of antibodies to insulin or its receptor is cited in literature as a very rare problem. One section in the differentially diagnostic thinking is dedicated to hypoglycemic states accompanying neoplastic, malign processes. Insulin is demonstrably not a responsible agent here, it is a polypeptide structurally close to it, a somatomedin abbreviated as IGF2. KEY WORDS: endoscopic ultrasound pancreatography (EUPG) - hypoglycemia mediated by tumour cells other than β cells (NIPHS) - insulin-like growth factor (IGF1, IGF2) - pro-insulin-like growth factor IGF2 (pro-IGF2).

• MeSH
• dospělí MeSH
• hyperinzulinismus etiologie   MeSH
• hypoglykemie etiologie   MeSH
• hypoglykemika terapeutické užití   MeSH
• inzulinom komplikace   diagnóza   MeSH
• lidé MeSH
• nádory slinivky břišní komplikace   diagnóza   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• hypoglykemika MeSH

Paraneoplastic hypoglyacemia (PH) is a relatively rare phenomenon, which may be caused by insulinomas or nonislet cell tumours (NICT). Both types are among the major "fasting" hypoglyacemia as opposed to reactive postprandial hypoglyacemia. The most common group of nonislet cell tumours causing hypoaglycemia are large mesenchymal tumours, which account for over 50 % of all neoplasms associated with hypoglyacemia. Neuroglycopenic symptoms in patients with NICT may be present for months or years before the actual diagnosis of the underlying disease. Differentiation and correct diagnosis of this type of disease leads to significant improvement in the quality of life of these patients.

• MeSH
• hypoglykemie etiologie   MeSH
• inzulinom komplikace   diagnóza   MeSH
• lidé MeSH
• nádory slinivky břišní komplikace   diagnóza   MeSH
• paraneoplastické syndromy diagnóza   MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• kazuistiky MeSH

Insulinomas are the most common functioning endocrine tumors of the pancreas. Most of them are well-differentiated tumors, with benign or uncertain behavior at the time of diagnosis. Surgery is considered to be the only curative treatment modality. We present the first case report of a 75-year-old woman with functioning insulinoma of the pancreatic body, which was destroyed by laparoscopic-assisted radiofrequency ablation. Hypoglycemic paroxysms disappeared immediately after surgery. The postoperative course was uneventful. The patient was discharged on the eighth postoperative day. There was a new onset of diabetes mellitus, without any further hypoglycemic paroxysm from surgery to the present-4 months. Laparoscopic-assisted radiofrequency ablation is shown to be a feasible and safe method for the treatment of functioning pancreatic insulinoma.

• MeSH
• diferenciální diagnóza MeSH
• inzulinom diagnóza   chirurgie   MeSH
• katetrizační ablace metody   MeSH
• laparoskopie metody   MeSH
• lidé MeSH
• nádory slinivky břišní diagnóza   chirurgie   MeSH
• pankreatektomie metody   MeSH
• počítačová rentgenová tomografie MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• audiovizuální média MeSH
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH

Insulin production in pancreatic beta-cells is critically linked to mitochondrial oxidative phosphorylation. Increased ATP production triggered by blood glucose represents the beta-cells' glucose sensor. Type-2 diabetes mellitus results from insulin resistance in peripheral tissues and impaired insulin secretion. Pathology of diabetic beta-cells might be reflected by the altered morphology of mitochondrial network. Its characterization is however hampered by the complexity and density of the three-dimensional (3D) mitochondrial tubular networks in these cell types. Conventional confocal microscopy does not provide sufficient axial resolution to reveal the required details; electron tomography reconstruction of these dense networks is still difficult and time consuming. However, mitochondrial network morphology in fixed cells can also be studied by 4Pi microscopy, a laser scanning microscopy technique which provides an approximately 7-fold improved axial resolution (approximately 100 nm) over conventional confocal microscopy. Here we present a quantitative study of these networks in insulinoma INS-1E cells and primary beta-cells in Langerhans islets. The former were a stably-transfected cell line while the latter were transfected with lentivirus, both expressing mitochondrial matrix targeted redox-sensitive GFP. The mitochondrial networks and their partial disintegration and fragmentation are revealed by carefully created iso-surface plots and their quantitative analysis. We demonstrate that beta-cells within the Langerhans islets from diabetic Goto Kakizaki rats exhibited a more disintegrated mitochondrial network compared to those from control Wistar rats and model insulinoma INS-1E cells. Standardization of these patterns may lead to development of morphological diagnostics for Langerhans islets, for the assessment of beta-cell condition, before their transplantations.

• MeSH
• beta-buňky patologie   ultrastruktura   MeSH
• diabetes mellitus 2. typu patologie   MeSH
• inzulinom patologie   MeSH
• konfokální mikroskopie metody   MeSH
• krysa rodu Rattus MeSH
• mitochondrie patologie   ultrastruktura   MeSH
• modely nemocí na zvířatech MeSH
• nádorové buněčné linie MeSH
• nádory slinivky břišní patologie   MeSH
• potkani Wistar MeSH
• rekombinantní fúzní proteiny genetika   MeSH
• techniky in vitro MeSH
• transfekce MeSH
• zelené fluorescenční proteiny genetika   MeSH
• zobrazování trojrozměrné MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• rekombinantní fúzní proteiny MeSH
• zelené fluorescenční proteiny MeSH

BACKGROUND: Organic hyperinsulinism causes hypoglycaemia manifesting mainly in the fasting state. We summarize our experience with diagnosis and treatment of 105 patients with organic hyperinsulinism. METHODS AND RESULTS: The diagnosis was confirmed in all patients by spontaneous hypoglycemia and neuroglycopenic symptoms, both developed during fasting test. Endoscopic ultrasonography was the most reliable method for the insulinoma localization (77% of insulinomas confirmed by surgery in the same location within the pancreas), less positive results were obtained by digital subtraction angiography (29%) and still less was found by computed tomography (18%). The localization remains unclear in about 20-25% of insulinomas despite of combined different exploring techniques. Surgical removal of insulinoma by enucleation is the best way of treatment, in some cases laparoscopic removal is a method of choice. From total number of 95 surgically treated patients the successful removal of insulinoma was performed in 84 patients (88%) and another 3 had histopathology diagnosis of micronodular polyadenomatosis. CONCLUSIONS: Insulinoma was not found during surgery and subsequent thorough histopathology investigation of the whole resecate in 8 patients which have to be treated like other non-surgically treated patients by diazoxide together with diabetic diet.

• MeSH
• dospělí MeSH
• hyperinzulinismus etiologie   MeSH
• inzulinom komplikace   diagnóza   terapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory slinivky břišní diagnóza   terapie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH

Increased ATP/ADP ratio resulting from enhanced glycolysis and oxidative phosphorylation represents a plausible mechanism controlling the glucose-stimulated insulin secretion (GSIS) in pancreatic beta-cells. Although specific bioenergetics might be involved, parallel studies of cell respiration and mitochondrial membrane potential (DeltaPsi(m)) during GSIS are lacking. Using high resolution respirometry and parallel DeltaPsi(m) monitoring by two distinct fluorescence probes we have quantified bioenergetics in rat insulinoma INS-1E cells representing a suitable model to study in vitro insulin secretion. Upon glucose addition to glucose-depleted cells we demonstrated a simultaneous increase in respiration and DeltaPsi(m) during GSIS and showed that the endogenous state 3/state 4 respiratory ratio hyperbolically increased with glucose, approaching the maximum oxidative phosphorylation rate at maximum GSIS. Attempting to assess the basis of the "toxic" effect of fatty acids on insulin secretion, GSIS was studied after linoleic acid addition, which diminished respiration increase, DeltaPsi(m) jump, and magnitude of insulin release, and reduced state 3/state 4 dependencies on glucose. Its effects were due to protonophoric function, i.e. uncoupling, since without glucose, linoleic acid accelerated both state 3 and state 4 respiration by similar extent. In turn, state 3 respiration increased marginally with linoleic acid at 10-20mM glucose. We conclude that upon glucose addition in physiological range, the INS-1E cells are able to regulate the oxidative phosphorylation rate from nearly zero to maximum and that the impairment of GSIS by linoleic acid is caused by mitochondrial uncoupling. These findings may be relevant to the pathogenesis of type 2 diabetes.

• MeSH
• adenosindifosfát metabolismus   MeSH
• adenosintrifosfát metabolismus   MeSH
• glukosa farmakologie   MeSH
• inzulinom metabolismus   MeSH
• krysa rodu Rattus MeSH
• kyselina linolová farmakologie   MeSH
• Langerhansovy ostrůvky účinky léků   metabolismus   MeSH
• membránový potenciál mitochondrií účinky léků   MeSH
• mitochondrie účinky léků   metabolismus   MeSH
• nádorové buňky kultivované MeSH
• nádory slinivky břišní metabolismus   MeSH
• potkani Wistar MeSH
• spotřeba kyslíku účinky léků   MeSH
• transmisní elektronová mikroskopie MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adenosindifosfát MeSH
• adenosintrifosfát MeSH
• glukosa MeSH
• kyselina linolová MeSH