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The Journal of Clinical Endocrinology... Mar 2024Insulinomas are hormone-producing pancreatic neuroendocrine neoplasms with an estimated incidence of 1 to 4 cases per million per year. Extrapancreatic insulinomas are...
Insulinomas are hormone-producing pancreatic neuroendocrine neoplasms with an estimated incidence of 1 to 4 cases per million per year. Extrapancreatic insulinomas are extremely rare. Most insulinomas present with the Whipple triad: (1) symptoms, signs, or both consistent with hypoglycemia; (2) a low plasma glucose measured at the time of the symptoms and signs; and (3) relief of symptoms and signs when the glucose is raised to normal. Nonmetastatic insulinomas are nowadays referred to as "indolent" and metastatic insulinomas as "aggressive." The 5-year survival of patients with an indolent insulinoma has been reported to be 94% to 100%; for patients with an aggressive insulinoma, this amounts to 24% to 67%. Five percent to 10% of insulinomas are associated with the multiple endocrine neoplasia type 1 syndrome. Localization of the insulinoma and exclusion or confirmation of metastatic disease by computed tomography is followed by endoscopic ultrasound or magnetic resonance imaging for indolent, localized insulinomas. Glucagon-like peptide 1 receptor positron emission tomography/computed tomography or positron emission tomography/magnetic resonance imaging is a highly sensitive localization technique for seemingly occult, indolent, localized insulinomas. Supportive measures and somatostatin receptor ligands can be used for to control hypoglycemia. For single solitary insulinomas, curative surgical excision remains the treatment of choice. In aggressive malignant cases, debulking procedures, somatostatin receptor ligands, peptide receptor radionuclide therapy, everolimus, sunitinib, and cytotoxic chemotherapy can be valuable options.
Topics: Humans; Insulinoma; Receptors, Somatostatin; Pancreatic Neoplasms; Hypoglycemia; Neuroendocrine Tumors
PubMed: 37925662
DOI: 10.1210/clinem/dgad641 -
Endocrine Jul 2023Secondary diabetes mellitus (DM) is a common complication of acromegaly, encountered in up to 55% of cases. Vice versa, the prevalence of acromegaly is markedly higher... (Review)
Review
Secondary diabetes mellitus (DM) is a common complication of acromegaly, encountered in up to 55% of cases. Vice versa, the prevalence of acromegaly is markedly higher in cohorts of patients with type 2 DM (T2DM). The presence of secondary DM depends primarily on acromegaly status and is associated with increased cardiovascular morbidity, malignancy rate and overall mortality. The principal pathophysiologic mechanism is increased insulin resistance due to excessive lipolysis and altered fat distribution, reflected at the presence of intermuscular fat and attenuated, dysfunctional adipose tissue. Insulin resistance is ascribed to the direct, diabetogenic effects of growth hormone (GH), which prevail over the insulin-sensitizing effects of insulin-like growth factor 1 (IGF-1), probably due to higher glucometabolic potency of GH, IGF-1 resistance, or both. Inversely, GH and IGF-1 act synergistically in increasing insulin secretion. Hyperinsulinemia in portal vein leads to enhanced responsiveness of liver GH receptors and IGF-1 production, pointing towards a mutually amplifying loop between GH-IGF-1 axis and insulin. Secondary DM occurs upon beta cell exhaustion, principally due to gluco-lipo-toxicity. Somatostatin analogues inhibit insulin secretion; especially pasireotide (PASI) impairs glycaemic profile in up to 75% of cases, establishing a separate pathophysiologic entity, PASI-induced DM. In contrast, pegvisomant and dopamine agonizts improve insulin sensitivity. In turn, metformin, pioglitazone and sodium-glucose transporters 2 inhibitors might be disease-modifying by counteracting hyperinsulinemia or acting pleiotropically. Large, prospective cohort studies are needed to validate the above notions and define optimal DM management in acromegaly.
Topics: Humans; Acromegaly; Insulin-Like Growth Factor I; Insulin Resistance; Prospective Studies; Human Growth Hormone; Growth Hormone; Insulin; Diabetes Mellitus
PubMed: 36882643
DOI: 10.1007/s12020-023-03339-1 -
The Journal of Clinical Endocrinology... Mar 2024Acromegaly treatment has greatly evolved in recent decades, but there are still patients whose acromegaly is not controlled with currently available treatments, and...
Acromegaly treatment has greatly evolved in recent decades, but there are still patients whose acromegaly is not controlled with currently available treatments, and there is a need to improve the treatment burden. Fortunately, there are new treatments under development that may increase treatment efficacy and convenience.
Topics: Humans; Acromegaly; Octreotide; Somatostatin; Peptides, Cyclic; Insulin-Like Growth Factor I
PubMed: 37757837
DOI: 10.1210/clinem/dgad568 -
Current Oncology Reports May 2024This paper aims to address the latest findings in neuroendocrine tumor (NET) theranostics, focusing on new evidence and future directions of combined diagnosis with... (Review)
Review
PURPOSE OF REVIEW
This paper aims to address the latest findings in neuroendocrine tumor (NET) theranostics, focusing on new evidence and future directions of combined diagnosis with positron emission tomography (PET) and treatment with peptide receptor radionuclide therapy (PRRT).
RECENT FINDINGS
Following NETTER-1 trial, PRRT with [177Lu]Lu-DOTATATE was approved by FDA and EMA and is routinely employed in advanced G1 and G2 SST (somatostatin receptor)-expressing NET. Different approaches have been proposed so far to improve the PRRT therapeutic index, encompassing re-treatment protocols, combinations with other therapies and novel indications. Molecular imaging holds a potential added value in characterizing disease biology and heterogeneity using different radiopharmaceuticals (e.g., SST and FDG) and may provide predictive and prognostic parameters. Response assessment criteria are still an unmet need and new theranostic pairs showed preliminary encouraging results. PRRT for NET has become a paradigm of modern theranostics. PRRT holds a favorable toxicity profile, and it is associated with a prolonged time to progression, reduction of symptoms, and improved patients' quality of life. In light of further optimization, different new strategies have been investigated, along with the development of new radiopharmaceuticals.
Topics: Humans; Neuroendocrine Tumors; Radiopharmaceuticals; Octreotide; Positron-Emission Tomography; Receptors, Peptide; Theranostic Nanomedicine; Radioisotopes; Organometallic Compounds
PubMed: 38581469
DOI: 10.1007/s11912-024-01526-5 -
Islets Dec 2023Somatostatin is a paracrine modulator of insulin secretion and beta cell function with pleotropic effects on glucose homeostasis. The mechanism of somatostatin-mediated...
Somatostatin is a paracrine modulator of insulin secretion and beta cell function with pleotropic effects on glucose homeostasis. The mechanism of somatostatin-mediated communication between delta and beta cells is not well-understood, which we address in this study via the ciliary somatostatin receptor 3 (SSTR3). Primary cilia are membrane organelles that act as signaling hubs in islets by virtue of their subcellular location and enrichment in signaling proteins such as G-protein coupled receptors (GPCRs). We show that SSTR3, a ciliary GPCR, mediates somatostatin suppression of insulin secretion in mouse islets. Quantitative analysis of calcium flux using a mouse model of genetically encoded beta cell-specific GCaMP6f calcium reporter shows that somatostatin signaling alters beta cell calcium flux after physiologic glucose stimulation, an effect that depends on endogenous SSTR3 expression and the presence of intact primary cilia on beta cells. Comparative studies using SSTR isoform antagonists demonstrate a role for SSTR3 in mediating somatostatin regulation of insulin secretion in mouse islets. Our findings support a model in which ciliary SSTR3 mediates a distinct pathway of delta-to-beta cell regulatory crosstalk and may serve as a target for paracrine modulation.
Topics: Cilia; Glucose; Receptors, Somatostatin; Somatostatin; Animals; Mice
PubMed: 37660302
DOI: 10.1080/19382014.2023.2252855 -
Cell Reports Aug 2023We sought to characterize the unique role of somatostatin (SST) in the prelimbic (PL) cortex in mice. We performed slice electrophysiology in pyramidal and GABAergic...
We sought to characterize the unique role of somatostatin (SST) in the prelimbic (PL) cortex in mice. We performed slice electrophysiology in pyramidal and GABAergic neurons to characterize the pharmacological mechanism of SST signaling and fiber photometry of GCaMP6f fluorescent calcium signals from SST neurons to characterize the activity profile of SST neurons during exploration of an elevated plus maze (EPM) and open field test (OFT). We used local delivery of a broad SST receptor (SSTR) agonist and antagonist to test causal effects of SST signaling. SSTR activation hyperpolarizes layer 2/3 pyramidal neurons, an effect that is recapitulated with optogenetic stimulation of SST neurons. SST neurons in PL are activated during EPM and OFT exploration, and SSTR agonist administration directly into the PL enhances open arm exploration in the EPM. This work describes a broad ability for SST peptide signaling to modulate microcircuits within the prefrontal cortex and related exploratory behaviors.
Topics: Animals; Mice; Exploratory Behavior; Somatostatin; Peptides; Calcium; GABAergic Neurons
PubMed: 37590138
DOI: 10.1016/j.celrep.2023.112976 -
International Journal of Molecular... Apr 2024Bivalves hold an important role in marine aquaculture and the identification of growth-related genes in bivalves could contribute to a better understanding of the...
Bivalves hold an important role in marine aquaculture and the identification of growth-related genes in bivalves could contribute to a better understanding of the mechanism governing their growth, which may benefit high-yielding bivalve breeding. Somatostatin receptor (SSTR) is a conserved negative regulator of growth in vertebrates. Although genes have been identified in invertebrates, their involvement in growth regulation remains unclear. Here, we identified seven s (s) in the Yesso scallop, , which is an economically important bivalve cultured in East Asia. Among the three s (, , and ) expressed in adult tissues, showed significantly lower expression in fast-growing scallops than in slow-growing scallops. Then, the function of this gene in growth regulation was evaluated in dwarf surf clams (), a potential model bivalve cultured in the lab, via RNA interference (RNAi) through feeding the clams containing plasmids expressing double-stranded RNAs (dsRNAs) targeting . Suppressing the expression of , the homolog of in , resulted in a significant increase in shell length, shell width, shell height, soft tissue weight, and muscle weight by 20%, 22%, 20%, 79%, and 92%, respectively. A transcriptome analysis indicated that the up-regulated genes after expression inhibition were significantly enriched in the fat digestion and absorption pathway and the insulin pathway. In summary, we systemically identified the s in and revealed the growth-inhibitory role of in bivalves. This study indicates the conserved function of somatostatin signaling in growth regulation, and ingesting dsRNA-expressing bacteria is a useful way to verify gene function in bivalves. is a candidate target for gene editing in bivalves to promote growth and could be used in the breeding of fast-growing bivalves.
Topics: Animals; Pectinidae; Bivalvia; Receptors, Somatostatin; Phylogeny; RNA Interference; Gene Expression Regulation, Developmental
PubMed: 38732036
DOI: 10.3390/ijms25094813 -
Cancers Nov 2023Lung carcinoids are neuroendocrine tumors, categorized as typical or atypical carcinoids based on their histological appearance. While most of these tumors are... (Review)
Review
Lung carcinoids are neuroendocrine tumors, categorized as typical or atypical carcinoids based on their histological appearance. While most of these tumors are slow-growing neoplasms, they still possess malignant potential. Many patients are diagnosed incidentally on chest X-rays or CT scans. Presenting symptoms include cough, hemoptysis, wheezing, dyspnea, and recurrent pneumonia. Endocrine symptoms, such as carcinoid syndrome or ectopic Cushing's syndrome, are rare. Surgery is the primary treatment and should be considered in all patients with localized disease, even when thoracic lymph node metastases are present. Patients with distant metastases may be treated with somatostatin analogues, chemotherapy, preferably temozolomide-based, mTOR inhibitors, or peptide receptor radionuclide therapy (PRRT) with Lu-DOTATATE. Most patients have an excellent prognosis. Poor prognostic factors include atypical histology and lymph node metastases at diagnosis. Long-term follow-up is mandatory since metastases may occur late.
PubMed: 38001701
DOI: 10.3390/cancers15225440