1.A focal form of diazoxide-resistant congenital hyperinsulinism with good response to long-acting somatostatin
Suhaimi Hussain ; Nurshafinaz Salmah Mohd Fezal ; Sarah Flanagan
Journal of the ASEAN Federation of Endocrine Societies 2024;39(2):108-111
A four-year-old female who was born term via spontaneous vaginal delivery with a birth weight of 3.4 kg had an onset of persistent hypoglycaemia at the 6th hour of life. She was diagnosed with congenital hyperinsulinism based on high glucose load, negative ketone and a good response to glucagon. Genetic workup revealed the presence of ATP Binding Cassette Subfamily C Member 8 (ABCC8 genes) mutation which indicated a focal form of congenital hyperinsulinism. She was resistant to the standard dose of oral diazoxide but responded to subcutaneous somatostatin. At the age of 3 years and 6 months, multiple daily injections of somatostatin were replaced with a long-acting monthly somatostatin analogue. With the present treatment, she had better glycaemic control, normal growth and was able to stop tube feeding.
Congenital Hyperinsulinism
;
Somatostatin
2.Somatostatin-Positive Neurons in the Rostral Zona Incerta Modulate Innate Fear-Induced Defensive Response in Mice.
Shan LIN ; Meng-Yue ZHU ; Meng-Yu TANG ; Mi WANG ; Xiao-Dan YU ; Yi ZHU ; Shi-Ze XIE ; Dan YANG ; Jiadong CHEN ; Xiao-Ming LI
Neuroscience Bulletin 2023;39(2):245-260
Defensive behaviors induced by innate fear or Pavlovian fear conditioning are crucial for animals to avoid threats and ensure survival. The zona incerta (ZI) has been demonstrated to play important roles in fear learning and fear memory, as well as modulating auditory-induced innate defensive behavior. However, whether the neuronal subtypes in the ZI and specific circuits can mediate the innate fear response is largely unknown. Here, we found that somatostatin (SST)-positive neurons in the rostral ZI of mice were activated by a visual innate fear stimulus. Optogenetic inhibition of SST-positive neurons in the rostral ZI resulted in reduced flight responses to an overhead looming stimulus. Optogenetic activation of SST-positive neurons in the rostral ZI induced fear-like defensive behavior including increased immobility and bradycardia. In addition, we demonstrated that manipulation of the GABAergic projections from SST-positive neurons in the rostral ZI to the downstream nucleus reuniens (Re) mediated fear-like defensive behavior. Retrograde trans-synaptic tracing also revealed looming stimulus-activated neurons in the superior colliculus (SC) that projected to the Re-projecting SST-positive neurons in the rostral ZI (SC-ZIrSST-Re pathway). Together, our study elucidates the function of SST-positive neurons in the rostral ZI and the SC-ZIrSST-Re tri-synaptic circuit in mediating the innate fear response.
Mice
;
Animals
;
Zona Incerta/metabolism*
;
Neurons/metabolism*
;
Fear/physiology*
;
Somatostatin/metabolism*
3.Spatial and temporal expression pattern of somatostatin receptor 2 in mouse.
Mingchuan TANG ; Chuan LIU ; Rongyu LI ; Huisang LIN ; Yanli PENG ; Yiming LANG ; Kecao SU ; Zhongliang XIE ; Mingyue LI ; Xiao YANG ; Guan YANG ; Xinjiong FAN ; Yan TENG
Chinese Journal of Biotechnology 2023;39(7):2656-2668
Somatostatin (SST) is an inhibitory polypeptide hormone that plays an important role in a variety of biological processes. Somatostatin receptor 2 (SSTR2) is the most widely expressed somatostatin receptor. However, the specific cell types expressing Sstr2 in the tissues have not been investigated. In this study, we detected the expression pattern of SSTR2 protein in mouse at different development stages, including the embryonic 15.5 days and the postnatal 1, 7, 15 days as well as 3 and 6 months, by multicolour immunofluorescence analyses. We found that Sstr2 was expressed in some specific cells types of several tissues, including the neuronal cells and astrocytes in the brain, the mesenchymal cells, the hematopoietic cells, the early hematopoietic stem cells, and the B cells in the bone marrow, the macrophages, the type Ⅱ alveolar epithelial cells, and the airway ciliated cells in the lung, the epithelial cells and the neuronal cells in the intestine, the hair follicle cells, the gastric epithelial cells, the hematopoietic stem cells and the nerve fibre in the spleen, and the tubular epithelial cells in the kidney. This study identified the specific cell types expressing Sstr2 in mouse at different developmental stages, providing new insights into the physiological function of SST and SSTR2 in several cell types.
Mice
;
Animals
;
Receptors, Somatostatin/metabolism*
;
Hematopoietic Stem Cells/metabolism*
;
Epithelial Cells
4.Effect of somatostatin on gastrointestinal hormone levels and clinical outcomes in critically ill infants after gastrointestinal surgery: a prospective randomized controlled study.
Bo-Xiang QI ; Zhi LIU ; Lei ZHU ; Li-Ping SHENG ; Shuang-Shuang HU ; Na-Na WEN ; Tong QIAN
Chinese Journal of Contemporary Pediatrics 2023;25(10):995-1000
OBJECTIVES:
To explore the effects of somatostatin on the levels of gastrointestinal hormones and clinical outcomes in critically ill infants after gastrointestinal surgery.
METHODS:
Using a random number table method, critically ill infants after gastrointestinal surgery who were admitted to the Intensive Care Unit of Xuzhou Children's Hospital from June 2019 to June 2021 were randomly divided into an observation group (29 cases) and a control group (30 cases). The control group received routine treatment such as anti-infection and hemostasis after surgery, while the observation group received somatostatin in addition to the routine treatment [3.5 μg/(kg·h) infusion for 7 days]. The levels of serum gastrin (GAS), motilin (MTL), insulin, and glucagon-like peptide-1 (GLP-1) before surgery, on the 3rd day after surgery, and on the 7th day after surgery were compared between the two groups. The recovery progress and incidence of complications after surgery were also compared between the two groups.
RESULTS:
There was no significant difference in the levels of serum GAS, MTL, insulin, and GLP-1 between the two groups before surgery (P>0.05). On the 3rd and 7th day after surgery, the levels of serum GAS, MTL, insulin, and GLP-1 in the observation group were higher than those in the control group (P<0.05). In the observation group, the levels of GAS, MTL, insulin, and GLP-1 on the 7th day after surgery were higher than those before surgery and on the 3rd day after surgery (P<0.05), and the levels on the 3rd day after surgery were higher than those before surgery (P<0.05). There was no significant difference in the levels of serum GAS, MTL, and insulin before surgery, on the 3rd day after surgery, and on the 7th day after surgery in the control group (P>0.05). The level of GLP-1 on the 7th day after surgery was higher than that before surgery and on the 3rd day after surgery (P<0.05), and the level on the 3rd day after surgery was higher than that before surgery (P<0.05) in the control group. The observation group had shorter first time of anal exhaust, recovery time of bowel sounds, and first time of defecation after surgery compared to the control group (P<0.05). The incidence of complications after surgery in the observation group was lower than that in the control group (10% vs 33%, P<0.05).
CONCLUSIONS
Somatostatin can increase the levels of serum GAS, MTL, insulin, and GLP-1 in critically ill infants after gastrointestinal surgery, promote the recovery of gastrointestinal function, and reduce the incidence of postoperative complications.
Humans
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Infant
;
Critical Illness
;
Digestive System Surgical Procedures
;
Glucagon-Like Peptide 1
;
Insulin
;
Prospective Studies
;
Somatostatin/therapeutic use*
5.Effect of somatostatin on postoperative gastrointestinal function and stress level in children with acute abdomen: a prospective randomized controlled study.
Bo-Xiang QI ; Lei ZHU ; Li-Ping SHENG ; Na-Na WEN ; Xiao CHENG ; Shuang-Shuang HU ; Tong QIAN
Chinese Journal of Contemporary Pediatrics 2022;24(7):812-816
OBJECTIVES:
To study the effect of somatostatin on postoperative gastrointestinal function and stress level in children with acute abdomen.
METHODS:
A total of 102 children with acute abdomen who underwent surgery in Xuzhou Children's Hospital from August 2019 to June 2021 were enrolled as subjects and were randomly divided into an observation group and a control group, with 51 children in each group. The children in the control group were given conventional treatment such as hemostasis and anti-infective therapy after surgery, and those in the observation group were given somatostatin in addition to conventional treatment. Peripheral blood samples were collected from both groups before surgery and on days 1 and 5 after surgery. The two groups were compared in terms of the serum levels of endothelin-1 (ET-1), adrenocorticotropic hormone (ACTH), cortisol, gastrin, and motilin, postoperative recovery, and the incidence rate of complications.
RESULTS:
There was no significant difference in the serum levels of ET-1, ACTH, cortisol, gastrin, and motilin between the two groups before surgery (P>0.05). Compared with the control group, the observation group had significantly lower serum levels of ET-1, ACTH, and cortisol on days 1 and 5 after surgery (P<0.05) and significantly higher levels of motilin and gastrin on day 5 after surgery (P<0.05). Compared with the control group, the observation group had significantly shorter time to first passage of flatus, first bowel sounds, and first defecation after surgery, as well as a significantly shorter length of hospital stay (P<0.05). The incidence rate of complications in the observation group was significantly lower than that in the control group (6% vs 24%, P<0.05).
CONCLUSIONS
In children with acute abdomen, somatostatin can significantly reduce postoperative stress response, improve gastrointestinal function, and reduce the incidence rate of complications, thereby helping to achieve a good prognosis.
Abdomen
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Abdomen, Acute
;
Adrenocorticotropic Hormone
;
Child
;
Gastrins
;
Humans
;
Hydrocortisone
;
Motilin
;
Postoperative Complications
;
Prospective Studies
;
Somatostatin/therapeutic use*
6.Auditory response patterns of mouse primary auditory cortex to sound stimuli.
Qin Hong ZHENG ; Chang Bao SONG ; Fei Xue LIANG
Journal of Southern Medical University 2022;42(8):1212-1220
OBJECTIVE:
To investigate the auditory response patterns of mouse primary auditory cortex (A1) neurons.
METHODS:
In vivo cell-attached recordings and neural network modeling were performed to detect the changes in response patterns of A1 neurons of awake C57BL/6J mice to sound stimulation with varying lengths. A1 neuron signals were recorded for 216 neurons in 20 awake mice using a target sound stimulation sequence, and the classification and response characteristics of A1 neuron response patterns were examined using post-stimulus spike time histograms. To simulate the diversity of the A1 neuron response patterns, an A1 neuron model was established based on the Wilson-Cowan model and integral-firing model. The neuron connection weight parameters in the model were calculated by examining the micro loop structure of the pyramidal neurons, parvalbumin neurons, and somatostatin neurons in the A1 region, and the A1 neural network information coding model was constructed.
RESULTS:
The Onset response neurons only had fast spike response within 10 to 40 ms after the beginning of noise stimulation (122 neurons). The Sustained response neurons had spike response continuously during the noise stimulation (26 neurons). The On-off response neurons had fast spike response after the beginning and the end of noise stimulation (40 neurons). The Offset response neurons only had fast spike response within 10 to 40 ms after the end of noise stimulation (22 neurons). In the neural network model, the Onset peak neural activities of A1 pyramidal neurons, parvalbumin neurons, and somatostatin neurons were 0.7483, 0.5236 and 0.9427, respectively, and their response half peak widths were 18.5 ms, 12 ms and 31 ms during the 100 ms noise stimulation, respectively. By changing the feedforward excitation and synaptic inhibition time constants in the model, the neurons generated numerous different types of spike train.
CONCLUSION
The auditory response of mouse A1 neurons to sound stimuli shows mainly the Onset, Sustained, On-off, and Offset response patterns.
Acoustic Stimulation
;
Animals
;
Auditory Cortex/physiology*
;
Mice
;
Mice, Inbred C57BL
;
Parvalbumins
;
Somatostatin
7.Cortical 5-hydroxytryptamine receptor 3A (Htr3a) positive inhibitory neurons: diversity in type and function.
Jin-Yun WU ; Hong-Zhi LIU ; Yan-Qing QI ; Xiao-Yang WU ; Yang CHEN ; Jiang-Teng LYU ; Ling GONG ; Miao HE
Acta Physiologica Sinica 2021;73(2):295-305
Cortical GABAergic inhibitory neurons are composed of three major classes, each expressing parvalbumin (PV), somatostatin (SOM) and 5-hydroxytryptamine receptor 3A (Htr3a), respectively. Htr3a
Animals
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Interneurons/metabolism*
;
Mice
;
Neurons/metabolism*
;
Parvalbumins/metabolism*
;
Receptors, Serotonin, 5-HT3/genetics*
;
Serotonin
;
Somatostatin/metabolism*
8.Mu-opioid receptors in the paraventricular nucleus regulate ejaculatory behaviors via the sympathetic nerve system in male rats.
Qi-Jie ZHANG ; Jiao-Chen LUAN ; Ya-Min WANG ; Ning-Hong SONG ; Jia-Dong XIA
National Journal of Andrology 2020;26(10):867-874
Objective:
To explore the effects of the mu-opioid receptor (MOR) in the paraventricular nucleus (PVN) on the ejaculatory behaviors of male rats and its potential mechanisms.
METHODS:
Male SD rats with normal ejaculation ability were mated with female ones in hormone-induced estrus. After bilateral PVN microinjection of D-Ala-2-Me-Phe-4-Gly-ol enkephalin (DAGO) or D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) with an inserted catheter, the male animals were observed for mount latency (ML), mount frequency (MF), intromission latency (IL), intromission frequency (IF), ejaculation latency (EL), ejaculation frequency (EF), post-ejaculation interval (PEI), and intromission ratio (IR). The lumbar sympathetic nerve activity (LSNA) of the rats was recorded using the PowerLab data acquisition hardware device, and the levels of norepinephrine (NE) in the peripheral plasma were measured by ELISA following microinjection of saline or different doses of DAGO or CTAP.
RESULTS:
Neither CTAP nor DGAO significantly affected the ML of the male rats (P > 0.05). DGAO remarkably increased IF (P < 0.01) and MF (P < 0.01), prolonged IL (P < 0.01), EL (P < 0.01) and PEI (P < 0.01), and reduced EF (P <0.01) and IR (P < 0.05). On the contrary, CTAP markedly decreased IF (P < 0.01) and MF (P < 0.01), shortened IL (P < 0.01), EL (P < 0.01) and PFI (P < 0.01), and elevated EF (P < 0.01) and IR (P < 0.01). Additionally, DAGO decreased LSNA in a dose-dependent manner and reduced the NE level in the peripheral plasma. CTAP, however, not only offset the effects of DAGO on LSNA, but also significantly increased LSNA.
CONCLUSIONS
MOR in PVN inhibits ejaculatory behaviors in male rats by weakening LSNA, which has provided some theoretical evidence for the use of highly selective opioids in the treatment of premature ejaculation.
Animals
;
Ejaculation
;
Enkephalin, Ala(2)-MePhe(4)-Gly(5)-/pharmacology*
;
Female
;
Male
;
Paraventricular Hypothalamic Nucleus/physiology*
;
Peptide Fragments/pharmacology*
;
Rats
;
Rats, Sprague-Dawley
;
Receptors, Opioid, mu/physiology*
;
Somatostatin/pharmacology*
;
Sympathetic Nervous System/physiology*
9.Recent Updates in the Management of Advanced Pancreatic Neuroendocrine Tumors
The Korean Journal of Gastroenterology 2019;73(3):124-131
Pancreatic neuroendocrine tumors (pNETs) are rare neoplasms arising from the pancreatic islet of Langerhans and can be functioning or non-functioning based on the clinical symptoms caused by hormonal secretions. PNETs are the second most common tumor of the pancreas and represent 1–2% of all pancreatic neoplasms. The incidence of pNETs appears to be rising and the prognosis seems to be improving, likely due to the improved treatment options. Recent updates of the World Health Organization classification and grading separate pNETs into 2 broad categories according to the histopathologic criteria, including the Ki-67 proliferative index and mitotic counts: well-differentiated NET and poorly-differentiated neuroendocrine carcinoma (NEC). The classification also incorporates a new subcategory of well-differentiated high-grade NEC (grade 3) to the well-differentiated NET category. This new classification algorithm aims to improve the prediction of the clinical outcomes and survival and help clinicians select better therapeutic strategies for patient care and management. The treatment of advanced or metastatic pNETs may include surgical resection, liver-directed therapies, and/or systemic treatments. In unresectable patients, the goals of these therapies are to palliate the tumor-related symptoms and prolong the lifespan. Systemic therapy consists of the following broad modalities: somatostatin analogues, molecular targeted therapy, systemic chemotherapy, and peptide receptor radionuclide therapy. In conclusion, pNETs are diagnosed increasingly throughout the world, usually with metastatic disease and requiring systemic therapy. Each patient should be evaluated thoroughly and discussed individually by a multidisciplinary and dedicated NET-expert team, which might consider all treatment options, including ongoing clinical trials before selecting the appropriate treatment sequence.
Carcinoma, Neuroendocrine
;
Classification
;
Drug Therapy
;
Humans
;
Incidence
;
Islets of Langerhans
;
Molecular Targeted Therapy
;
Neuroectodermal Tumors, Primitive
;
Neuroendocrine Tumors
;
Pancreas
;
Pancreatic Neoplasms
;
Patient Care
;
Prognosis
;
Receptors, Peptide
;
Somatostatin
;
World Health Organization
10.Medical Treatment with Somatostatin Analogues in Acromegaly: Position Statement
Sang Ouk CHIN ; Cheol Ryong KU ; Byung Joon KIM ; Sung Woon KIM ; Kyeong Hye PARK ; Kee Ho SONG ; Seungjoon OH ; Hyun Koo YOON ; Eun Jig LEE ; Jung Min LEE ; Jung Soo LIM ; Jung Hee KIM ; Kwang Joon KIM ; Heung Yong JIN ; Dae Jung KIM ; Kyung Ae LEE ; Seong Su MOON ; Dong Jun LIM ; Dong Yeob SHIN ; Se Hwa KIM ; Min Jeong KWON ; Ha Young KIM ; Jin Hwa KIM ; Dong Sun KIM ; Chong Hwa KIM
Korean Journal of Medicine 2019;94(6):485-494
Acromegaly is a chronic disorder caused by excessive growth hormone (GH) secretion. In most cases, the excess GH originates from GH-producing pituitary adenomas. Surgery is the preferred first-line treatment for patients with acromegaly, but medical management is considered when the disease persists after surgery or in cases where patients refuse surgery or are poor candidates for surgery. Somatostatin analogues are commonly used to treat acromegaly. The Korean Endocrine Society and the Korean Neuroendocrine Study Group have developed a position statement for the use of somatostatin analogues in the medical treatment of acromegaly. This position statement is based on evidence from the current literature and expert opinions. In the case of discrepancies among expert opinions, the experts voted to determine the recommended approach.
Acromegaly
;
Expert Testimony
;
Growth Hormone
;
Humans
;
Octreotide
;
Pituitary Neoplasms
;
Somatostatin


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