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Case Reports in Endocrinology 2022This rare case vignette describes hypoglycemic, hyperinsulinemic nesidioblastosis in a female patient with prior Roux-en-Y gastric bypass. The patient presented with...
This rare case vignette describes hypoglycemic, hyperinsulinemic nesidioblastosis in a female patient with prior Roux-en-Y gastric bypass. The patient presented with severe symptomatic hypoglycemia resistant to IV dextrose and diazoxide, requiring surgical resection. Traditional imaging found nonspecific findings, and biochemical analysis was inconsistent with insulinoma. A gallium-68 dotatate PET scan was utilized to successfully localize the tumor in the distal pancreas. She underwent laparoscopic resection of the distal pancreatic lesion with resolution of her symptoms and return to euglycemia. The histological evaluation confirmed the diagnosis of nesidioblastosis. Nesidioblastosis is a rare complication of bariatric surgery that may be more clinically relevant with rising prevalence of obesity. Diagnosis with conventional imaging modalities may be challenging; however, the dotatate PET scan may have high utility in detecting lesions. It is essential for clinicians to consider nesidioblastosis in the differential diagnosis of hyperinsulinemic hypoglycemic conditions and recognize there may be a link with increasing rates of bariatric surgery.
PubMed: 36588628
DOI: 10.1155/2022/5472304 -
JFMS Open Reports 2022A 5.5 month-old intact male Maine Coon cat was presented to a referral hospital for a history of muscle fasciculations, lethargy and seizures associated with refractory...
CASE SUMMARY
A 5.5 month-old intact male Maine Coon cat was presented to a referral hospital for a history of muscle fasciculations, lethargy and seizures associated with refractory hypoglycemia. Diagnostic testing for hypothyroidism, hyposomatotropism or hypoadrenocorticism, inborn errors of metabolism (ie, storage diseases and urea cycle disorders), infection or iatrogenic hypoglycemia were negative. An inappropriately high serum insulin level was noted in the face of marked hypoglycemia. The insulin:glucose ratio was 0.44 (<0.3) and the amended insulin:glucose ratio was 1268 (<30). Thoracic radiography and abdominal ultrasonography did not identify a cause for this elevated insulin level. Stabilization with a low, but adequate, blood glucose occurred with corticosteroid therapy, with further significant improvement with the addition of diazoxide. Peripheral neuropathy developed several months later, and concerns for quality of life led to humane euthanasia approximately 1 year after the initial diagnosis. Insulin levels remained high at the time of euthanasia. Necropsy found no gross lesions, though microscopic degeneration of the sciatic nerve and subjectively mildly increased size and number of pancreatic islets was noted. These findings were consistent with a diagnosis of congenital hyperinsulinism.
RELEVANCE AND NOVEL INFORMATION
This is the first reported case of congenital hyperinsulinism in a cat and may parallel the diffuse form of hypoglycemic hyperinsulinism reported in humans and a single dog. It should be considered a differential diagnosis in kittens presenting for refractory hypoglycemia.
PubMed: 36458207
DOI: 10.1177/20551169221136473 -
Endocrinology, Diabetes & Metabolism... Nov 2022A 52-year-old female presented with recurrent episodes of fasting or post-absorptive hypoglycemia. A 72-h fasting test confirmed endogenous hyperinsulinemia....
SUMMARY
A 52-year-old female presented with recurrent episodes of fasting or post-absorptive hypoglycemia. A 72-h fasting test confirmed endogenous hyperinsulinemia. Conventional imaging was unremarkable. Selective pancreatic arterial calcium stimulation and hepatic venous sampling showed a maximum calcium-stimulated insulin concentration from several pancreatic areas, mainly the proximal splenic artery and the proximal gastroduodenal artery, suggesting the presence of one or more occult insulinoma(s) in the region of the pancreatic body. 68Ga-DOTA-exendin-4 PET/CT showed however generalized increased uptake in the pancreas and a diagnosis of nesidioblastosis was therefore suspected. The patient has been since successfully treated with dietetic measures and diazoxide. Treatment efficacy was confirmed by a flash glucose monitoring system with a follow-up of 7 months.
LEARNING POINTS
Adult nesidioblastosis is a rare cause of endogenous hyperinsulinemic hypoglycemia. The distinction between insulinoma and nesidioblastosis is essential since the therapeutic strategies are different. 68Ga-DOTA-exendin-4 PET/CT emerges as a new noninvasive diagnostic tool for the localization of an endogenous source of hyperinsulinemic hypoglycemia. Medical management with dietetic measures and diazoxide need to be considered as a valuable option to treat patients with adult nesidioblastosis. Flash glucose monitoring system is helpful for the evaluation of treatment efficacy.
PubMed: 36448840
DOI: 10.1530/EDM-22-0325 -
Hormone Research in Paediatrics 2022Congenital hyperinsulinism is the most common cause of persistent hypoglycemia in neonates, infants, and children. Since the first case descriptions in the 1950s, the... (Review)
Review
Congenital hyperinsulinism is the most common cause of persistent hypoglycemia in neonates, infants, and children. Since the first case descriptions in the 1950s, the field has advanced significantly. It was the development of the insulin radioimmunoassay by Yalow and Berson a decade later that made it possible to demonstrate that this form of persistent hypoglycemia was caused by insulin, and a few years later, Drash described the successful treatment of children with hyperinsulinism with the antihypertensive diazoxide, which until today remains the only approved treatment for hyperinsulinism. In the mid 1970s, Baker and Stanley described that hyperinsulinism can be recognized by inappropriate responses of metabolic fuels and hormones during the course of a provocative fasting challenge. Later, advances in molecular genetics led to the discovery of the different genetic subtypes of hyperinsulinism. One of the most impactful discoveries in the field was the recognition of the focal form of hyperinsulinism and the development of 18F-DOPA PET for the localization of focal lesions before surgery which has resulted in the possibility of cure for children with focal disease. However, treatment options for children with nonfocal diazoxide-unresponsive hyperinsulinism have continued to be limited. New drug development programs for hyperinsulinism promise to change this in the next few years. Unfortunately, despite all these advances, children with hyperinsulinism around the world continue to experience neurological sequelae at high rates, highlighting the importance of early diagnosis and effective treatment.
Topics: Child; Humans; Infant; Infant, Newborn; Antihypertensive Agents; Congenital Hyperinsulinism; Diazoxide; Insulin
PubMed: 36446321
DOI: 10.1159/000526442 -
Journal of the American Heart... Dec 2022Background ATP-sensitive potassium channels are inhibited by ATP and open during metabolic stress, providing endogenous myocardial protection. Pharmacologic opening of... (Review)
Review
Background ATP-sensitive potassium channels are inhibited by ATP and open during metabolic stress, providing endogenous myocardial protection. Pharmacologic opening of ATP potassium channels with diazoxide preserves myocardial function following prolonged global ischemia, making it an ideal candidate for use during cardiac surgery. We hypothesized that diazoxide would reduce myocardial stunning after regional ischemia with subsequent prolonged global ischemia, similar to the clinical situation of myocardial ischemia at the time of revascularization. Methods and Results Swine underwent left anterior descending occlusion (30 minutes), followed by 120 minutes global ischemia protected with hyperkalemic cardioplegia±diazoxide (N=6 each), every 20 minutes cardioplegia, then 60 minutes reperfusion. Cardiac output, time to wean from cardiopulmonary bypass, left ventricular (LV) function, caspase-3, and infarct size were compared. Six animals in the diazoxide group separated from bypass by 30 minutes, whereas only 4 animals in the cardioplegia group separated. Diazoxide was associated with shorter but not significant time to wean from bypass (17.5 versus 27.0 minutes; =0.13), higher, but not significant, cardiac output during reperfusion (2.9 versus 1.5 L/min at 30 minutes; =0.05), and significantly higher left ventricular ejection fraction at 30 minutes (42.5 versus 15.8%; <0.01). Linear mixed regression modeling demonstrated greater left ventricular developed pressure (<0.01) and maximum change in ventricular pressure during isovolumetric contraction (<0.01) in the diazoxide group at 30 minutes of reperfusion. Conclusions Diazoxide reduces myocardial stunning and facilitates separation from cardiopulmonary bypass in a model that mimics the clinical setting of ongoing myocardial ischemia before revascularization. Diazoxide has the potential to reduce myocardial stunning in the clinical setting.
Topics: Swine; Animals; Diazoxide; Myocardial Stunning; KATP Channels; Stroke Volume; Ventricular Function, Left; Ischemia; Myocardial Ischemia; Adenosine Triphosphate
PubMed: 36444837
DOI: 10.1161/JAHA.122.026304 -
Medicines (Basel, Switzerland) Nov 2022(green tea) is used in traditional medicine to treat a wide range of ailments. In the present study, the insulin-releasing and glucose-lowering effects of the ethanol...
Antidiabetic Actions of Ethanol Extract of Leaf Ameliorates Insulin Secretion, Inhibits the DPP-IV Enzyme, Improves Glucose Tolerance, and Increases Active GLP-1 (7-36) Levels in High-Fat-Diet-Fed Rats.
(green tea) is used in traditional medicine to treat a wide range of ailments. In the present study, the insulin-releasing and glucose-lowering effects of the ethanol extract of (EECS), along with molecular mechanism/s of action, were investigated in vitro and in vivo. The insulin secretion was measured using clonal pancreatic BRIN BD11 β cells, and mouse islets. In vitro models examined the additional glucose-lowering properties of EECS, and 3T3L1 adipocytes were used to assess glucose uptake and insulin action. Non-toxic doses of EECS increased insulin secretion in a concentration-dependent manner, and this regulatory effect was similar to that of glucagon-like peptide 1 (GLP-1). The insulin release was further enhanced when combined with isobutylmethylxanthine (IBMX), tolbutamide or 30 mM KCl, but was decreased in the presence of verapamil, diazoxide and Ca chelation. EECS also depolarized the β-cell membrane and elevated intracellular Ca, suggesting the involvement of a K-dependent pathway. Furthermore, EECS increased glucose uptake and insulin action in 3T3-L1 cells and inhibited dipeptidyl peptidase IV (DPP-IV) enzyme activity, starch digestion and protein glycation in vitro. Oral administration of EECS improved glucose tolerance and plasma insulin as well as inhibited plasma DPP-IV and increased active GLP-1 (7-36) levels in high-fat-diet-fed rats. Flavonoids and other phytochemicals present in EECS could be responsible for these effects. Further research on the mechanism of action of EECS compounds could lead to the development of cost-effective treatments for type 2 diabetes.
PubMed: 36422117
DOI: 10.3390/medicines9110056 -
Scientific Reports Nov 20224-tert-Octylphenol (4-tOP) is a component of non-ionic surfactants alkylphenol polyethoxylates while triclosan (TCS) is an antibacterial present in personal care...
4-tert-Octylphenol (4-tOP) is a component of non-ionic surfactants alkylphenol polyethoxylates while triclosan (TCS) is an antibacterial present in personal care products. Both compounds can co-exist in environmental matrices such as soil and water. The mixture effects of these micropollutants in vitro remains unknown. INS-1 cells were exposed to 20 µM or 30 µM 4-tOP and 8 µM or 12.5 µM TCS as well as equimolar mixture of the chemicals (Mix) in total concentration of 12.5 µM or 25 µM for 48 h. Mitochondrial related parameters were investigated using high content analytical techniques. The cytotoxicity of the chemicals (IC) varied according to TCS > Mix > 4-tOP. Increased glucose uptake and loss of mitochondrial membrane potential were recorded in TCS and Mix treated cells. Fold values of glucose-galactose assay varied according to dinitrophenol > TCS > 4-tOP > Mix in decreasing order of mitochondrial toxicity. The loss of the intracellular Ca influx by all the test substances and Mix was not substantial whereas glibenclamide and diazoxide increased the intracellular Ca influx when compared with the Blank. The recorded increase in Ca influx by diazoxide which contrasted with its primary role of inhibiting insulin secretion need be re-investigated. It is concluded that the toxic effects of TCS and Mix but not 4-tOP on INS-1 cells was mitochondria-mediated.
Topics: Endocrine Disruptors; Diazoxide; Triclosan; Mitochondria; Biological Assay
PubMed: 36418342
DOI: 10.1038/s41598-022-20655-0 -
Pediatric Reports Oct 2022: Hyperinsulinemic hypoglycemia (HH) is an important cause of persistent hypoglycemia in newborns and infants. Recently, (phosphomannomutase 2) mutation has been...
: Hyperinsulinemic hypoglycemia (HH) is an important cause of persistent hypoglycemia in newborns and infants. Recently, (phosphomannomutase 2) mutation has been associated with HH, especially in conjunction with polycystic kidney disease (PKD). deficiency is one of the most common causes of congenital disorder of glycosylation (CDG). Renal involvement in PMM2-CDG manifests as cystic kidney disease, echogenic kidneys, nephrotic syndrome or mild proteinuria. : Here, we describe a pair of siblings with HH associated with autosomal recessive polycystic kidney disease (ARPKD) and mutation. Two siblings with ARPKD presented during infancy and early toddler years with severe hypoglycemia. Both had inappropriately elevated serum insulin, low β-hydroxybutyrate, a need for a high glucose infusion rate, positive glycemic response to glucagon, positive diazoxide response and mutation. : Although this combination of HH and PKD was recently described in patients of European descent who also had mutation, our report is unique given that these non-consanguineous siblings were not exclusively of European descent. mutation leading to abnormal glycosylation and causing cystic kidneys and the alteration of insulin secretion is the most likely pathogenesis of this clinical spectrum.
PubMed: 36412659
DOI: 10.3390/pediatric14040052 -
Journal of Traditional Chinese Medicine... Dec 2022To evaluate the protective effects of serum containing Dangua Fang on vascular endothelium damaged by oxidative stress.
OBJECTIVE
To evaluate the protective effects of serum containing Dangua Fang on vascular endothelium damaged by oxidative stress.
METHODS
Five experiments were completed in this paper. In the first experiment, we found the most suitable serum containing Dangua Fang by comparing groups with different serum containing Dangua Fang. In the second experiments we analyzed Dangua Fang influencing endothelial cell viability and apoptosis and cell cycle. The third experiment on Dangua Fang intervention of mitochondrial respiratory chain. The fourth experiment on Dangua Fang intervention of mitochondrial membrane potential. And finally, on the fifth experiment we researched the mechanism of Dangua Fang improving mitochondrial function by comparing the Na-k-ATPase and peroxisome proliferator-activated receptor- gamma coactivator-1alpha (PGC-1α) in the Dangua group with the diazoxide group and Co Q+Vit C group.
RESULTS
We compared the control group in the first experiments and the OD values in DZ1 group was the most significant in all intervening groups. The recipe of DZ1 (5% serum containing Dangua Fang) was used in the following experiments. Compared with the control group, cell viability, cell cycle (G2 + S), cytochrome c oxidase (COX), R3 red/green, R2 red/green, R1 red/ green decreased and apoptosis, succinate dehy-drogenase (SDH), green (R2 + R3), Na-k-ATPase, PGC-1α increased in the model group. Compared with the model group, cell viability, G2+S, COX, R3 red/green, R2 red/green, R1 red/green raised and apoptosis, green (R2 + R3), Na-K-ATPase decreased in the Dangua group; G2 + S, R3 red/green, R2 red/green, R1 red/green raised and green (R2 + R3) decreased in the Co Q + Vit C group. Na-K-ATPase increased in the combined group ( 0.05 or < 0.01).
CONCLUSIONS
Dangua Fang protects oxidative stress-induced endothelial cells damaged by promotion of mitochondrial biogenesis, reduction of Na-K-ATPase activity and regulation of mitochondrial respiratory chain function restoring mitochondrial membrane potential.
Topics: Humans; Endothelial Cells; Transcription Factors; Oxidative Stress; Mitochondria; Adenosine Triphosphatases
PubMed: 36378047
DOI: 10.19852/j.cnki.jtcm.20220815.001 -
American Journal of Physiology. Heart... Dec 2022Mitochondrial numbers and dynamics in brain blood vessels differ between young male and female rats under physiological conditions, but how these differences are...
Mitochondrial numbers and dynamics in brain blood vessels differ between young male and female rats under physiological conditions, but how these differences are affected by stroke is unclear. In males, we found that mitochondrial numbers, possibly due to mitochondrial fission, in large middle cerebral arteries (MCAs) increased following transient middle cerebral artery occlusion (tMCAO). However, mitochondrial effects of stroke on MCAs of female rats have not been studied. To address this disparity, we conducted morphological, biochemical, and functional studies using electron microscopy, Western blot, mitochondrial respiration, and Ca sparks activity measurements in MCAs of female, naïve or sham Sprague-Dawley rats before and 48 h after 90 min of tMCAO. Adverse changes in mitochondrial characteristics and the relationship between mitochondria and sarcoplasmic reticulum (SR) in MCAs were present on both sides. However, mitochondria and mitochondrial/SR associations were often within the range of normal appearance. Mitochondrial protein levels were similar between ipsilateral (ipsi) and contralateral (contra) sides. Nonrespiratory oxygen consumption, maximal respiration, and spare respiratory capacity were similar between ipsi and contra but were reduced compared with sham. Basal respiration, proton leak, and ATP production were similar among MCAs. Ca sparks activity increased in sham and ipsi MCAs exposed to a mitochondrial ATP-sensitive potassium channel opener: diazoxide. Our results show that tMCAO has effects on mitochondria in MCAs on both the ipsi and contra sides. Mitochondrial responses of cerebral arteries to tMCAO in females are substantially different from responses seen previously in male rats suggesting the need for specific sex-based therapies. We propose that differences in mitochondrial characteristics of males and females, including mitochondrial morphology, respiration, and calcium sparks activity contribute to sex differences in protective and repair mechanisms in response to transient ischemia-reperfusion.
Topics: Female; Male; Rats; Animals; Ischemic Attack, Transient; Middle Cerebral Artery; Rats, Sprague-Dawley; Stroke
PubMed: 36367688
DOI: 10.1152/ajpheart.00346.2022