Somatostatin-Positive Neurons in the Rostral Zona Incerta Modulate Innate Fear-Induced Defensive Response in Mice / 神经科学通报·英文版

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.

Cortical 5-hydroxytryptamine receptor 3A (Htr3a) positive inhibitory neurons: diversity in type and function / 生理学报

Cortical GABAergic inhibitory neurons are composed of three major classes, each expressing parvalbumin (PV), somatostatin (SOM) and 5-hydroxytryptamine receptor 3A (Htr3a), respectively. Htr3a

Effectiveness of hip muscle strengthening in patellofemoral pain syndrome patients: a systematic review

Introduction: Patellofemoral pain syndrome (PFPS) is characterized by anterior knee pain, which may limit the performance of functional activities. The influence of hip joint motion on the development of this syndrome has already been documented in the literature. In this regard, studies have investigated the effectiveness of hip muscle strengthening in patients with PFPS. Objectives: The aims of this systematic review were (1) to summarize the literature related to the effects of hip muscle strengthening on pain intensity, muscle strength, and function in individuals with PFPS and (2) to evaluate the methodological quality of the selected studies. Method: A search for randomized controlled clinical trials was conducted using the following databases: Google Scholar, MEDLINE, PEDro, LILACS, and SciELO. The selected studies had to distinguish the effects of hip muscle strengthening in a group of patients with PFPS, as compared to non-intervention or other kinds of intervention, and had to investigate the following outcomes: pain, muscle strength, and function. The methodological quality of the selected studies was analyzed by means of the PEDro scale. Results: Seven studies were selected. These studies demonstrated that hip muscle strengthening was effective in reducing pain. However, the studies disagreed regarding the treatments' ability to improve muscle strength. Improvement in functional capabilities after hip muscle strengthening was found in five studies. Conclusion: Hip muscle strengthening is effective in reducing the intensity of pain and improving functional capabilities in patients with PFPS, despite the lack of evidence for its ability to increase muscle strength. .

Role of high mobility group box-1 and protection of growth hormone and somatostatin in severe acute pancreatitis

In this study, we investigated the potential role of high-mobility group box 1 (HMGB1) in severe acute pancreatitis (SAP) and the effects of growth hormone (G) and somatostatin (S) in SAP rats. The rats were randomly divided into 6 groups of 20 each: sham-operated, SAP, SAP+saline, SAP+G, SAP+S and SAP+G+S. Ileum and pancreas tissues of rats in each group were evaluated histologically. HMGB1 mRNA expression was measured by reverse transcription-PCR. Levels of circulating TNF-α, IL-1, IL-6, and endotoxin were also measured. In the SAP group, interstitial congestion and edema, inflammatory cell infiltration, and interstitial hemorrhage occurred in ileum and pancreas tissues. The levels of HMGB1, TNF-α, IL-1, IL-6 and endotoxin were significantly up-regulated in the SAP group compared with those in the sham-operated group, and the 7-day survival rate was 0%. In the SAP+G and SAP+S groups, the inflammatory response of the morphological structures was alleviated, the levels of HMGB1, TNF-α, IL-1, IL-6, and endotoxin were significantly decreased compared with those in the SAP group, and the survival rate was increased. Moreover, in the SAP+G+S group, all histological scores were significantly improved and the survival rate was significantly higher compared with the SAP group. In conclusion, HMGB1 might participate in pancreas and ileum injury in SAP. Growth hormone and somatostatin might play a therapeutic role in the inflammatory response of SAP.

Effect of a Denture Adhesive on the Satisfaction and Kinesiographic Parameters of Complete Denture Wearers: A Cross-Over Randomized Clinical Trial

The aim of the present study was to assess the effect of a denture adhesive (DA) on patient satisfaction and kinesiographic parameters of complete denture wearers by a cross-over study. Fifty edentulous patients received a set of new complete dentures. After an adaptation period, the participants were enrolled in the trial and randomized to receive a sequence of treatment protocols: Protocol 1- DA use during the first 15 days, followed by no DA for the next 15 days; Protocol 2- no DA during the first 15 days, followed by use of DA for the next 15 days. Outcomes were assessed after 15 days of each sequence of treatment. A questionnaire was used to assess the patients´ satisfaction. A kinesiograph was used to record mandible movements and patterns of maxillary complete denture movement during chewing. The Wilcoxon test (α=0.05) and a paired sample t-test (α=0.05) were used to compare satisfaction levels and kinesiographic data, respectively. Use of DA improved the overall level of patient satisfaction (p<0.001). The kinesiographic recordings revealed a significant increase (1.7 mm) in vertical mandible movements (p<0.001) during chewing and a lower (0.3 mm) vertical intrusion of the maxillary complete dentures (p=0.002) during chewing after using the DA. Use of DA in complete denture wearers improved the patients´ satisfaction and altered mandible movements, with increases in vertical movements during chewing and less intrusion of maxillary complete dentures.

O objetivo deste estudo foi avaliar o efeito da utilização de um adesivo para prótese na satisfação e nos parâmetros cinesiográficos em usuários de próteses totais por meio de um estudo "cross-over". Cinquenta pacientes desdentados receberam novas próteses totais bimaxilares. Após um período de adaptação, os participantes incluídos no estudo receberam uma sequência de tratamento: Protocolo 1- utilização do adesivo para prótese durante os primeiros 15 dias, seguida por não utilização do adesivo os próximos 15 dias; Protocolo 2- não utilização do adesivo durante os primeiros 15 dias; seguida por utilização do adesivo nos próximos 15 dias. Os resultados foram avaliados após 15 dias de cada sequência de tratamento. Um questionário para avaliar a satisfação dos pacientes e um cinesiógrafo para registrar os movimentos mandibulares e o padrão de movimento da prótese total maxilar durante mastigação foram utilizados. O teste de "Wilcoxon" (α=0,05) e o "t-test" de Student para amostras pareadas (α=0,05) foram utilizados para comparar o grau de satisfação dos pacientes e os dados cinesiográficos, respectivamente. O adesivo para prótese melhorou significativamente a satisfação geral dos participantes (p<0,001). Os registros cinesiográficos mostraram um aumento significativo (1,7 mm) no movimento mandibular vertical (p<0,001) e uma menor intrusão (0,3 mm) da prótese total superior (p=0,002) durante a mastigação após o uso de adesivo. O uso de adesivo para prótese melhorou a satisfação dos usuários de próteses totais e gerou um aumento no movimento mandibular vertical e uma menor intrusão da prótese total maxilar durante a mastigação.

Decrease in intestinal endocrine cells in Balb/c mice with CT-26 carcinoma cells

The density of intestinal endocrine cells, in Balb/c mice with colon 26 (CT-26) carcinoma cells, were examined immunohistochemically at 28 days after implantation. After CT-26 cell administration there was a significant decrease in most of the intestinal endocrine cells (p < 0.01) compared with the control group. The significant quantitative changes in the intestinal endocrine cell density might contribute to the development of the gastrointestinal symptoms commonly encountered in cancer patients.

Immunocytochemical study of the distribuition of endocrine cells in the pancreas of the Brazilian sparrow species Zonotrichia Capensis Subtorquata (Swaison, 1837)

In the present study, we investigated types of pancreatic endocrine cells and its respective peptides in the Brazilian sparrow species using immunocytochemistry. The use of polyclonal specific antisera for somatostatin, glucagon, avian pancreatic polypeptide (APP), YY polypeptide (PYY) and insulin, revealed a diversified distribution in the pancreas. All these types of immunoreactive cells were observed in the pancreas with different amounts. Insulin- Immunoreactive cells to (B cells) were most numerous, preferably occupying the central place in the pancreatic islets. Somatostatin, PPA, PYY and glucagon immunoreactive cells occurred in a lower frequency in the periphery of pancreatic islets.

Os tipos de células endócrinas e seus respectivos peptídeos reguladores foram estudados imunocitoquimicamente no pâncreas do tico-tico, espécie Zonotrichia capensis subtorquata, empregando-se o método imunocitoquímico ABC - Peroxidase (Complexo Avidina - Biotina - Peroxidase) e anti-soros específicos para somatostatina, ao glucagon, ao polipeptídeo pancreático aviário (PPA), ao polipeptídeo YY (PYY) e à insulina. Todos estes tipos de células imunorreativas foram observadas no pâncreas em quantidades diferentes. As células imunorreativas à insulina (células B) foram as mais numerosas, ocupando preferencialmente, a região central das ilhotas pancreáticas. As células endócrinas imunorreativas à somatostatina, PPA, PYY e glucagon localizaram-se predominantemente na periferia das ilhotas.

Immunohistochemical Study of the Endocrine Cells in the Pancreas of the Carp,Cyprinus carpio (Cyprinidae)

The regional distribution and relative frequency of some endocrine cells in the pancreas of the carp, Cyprinus carpio Linnaeus, belonging to the family Cyprinidae in the order Cypriniformes, were observed using specific mammalian antisera against insulin, glucagon, somatostatin and human pancreatic polypeptide (hPP) by peroxidase antiperoxidase (PAP) method. The pancreas was divided into four regions (principal and secondary islets, exocrine and pancreatic duct regions). In addition, the pancreatic islet regions were further subdivided into three regions (central, mantle and peripheral regions) and the pancreatic duct regions were subdivided into two regions (epithelial and subepithelial regions). Spherical to spindle or occasionally round to oval shaped immunoreactive (IR) cells were demonstrated in the pancreatic islets, exocrine and pancreatic duct. In the principal islet regions, some cells were also detected in the other regions, most of insulin- and somatostatin-IR cells were located in the central regions, and glucagon- and hPP-IR cells were situated in the peripheral regions. In this regions, insulin-IR cells were most predominant cell types and then, glucagon, somatostatin and hPP in that order. In the secondary islet regions, the regional distribution and relative frequency of these four types of endocrine cells were quite similar to those of the principal islets except for cell clusters consisted of hPP-IR cells that were situated in the peripheral to mantle regions. In the pancreatic duct regions, all four major pancreatic endocrine cells were demonstrated in the inter-epithelial cells and/or basal regions of the epithelial linning. In addition, cell clusters composed of numerous insulin-, moderate glucagon- and somatostatin-IR cells of low frequency were also observed in the subepithelial regions of the pancreatic duct. In the exocrine regions, insulin-, glucagon-, somatostatin- and hPP-IR cells were located in the inter-acinus regions with rare, a few, moderate and moderate frequencies, respectively. In conclusion, the regional distribution and relative frequency of four major pancreatic endocrine cells, insulin-, glucagon-, somatostatin- and hPP-IR cells, in the pancreas of the carp showed general patterns which were observed in other stomachless teleost. However, some species- dependent different distributional patterns and/or relative frequencies were also demonstrated.

An immunohistochemical Study on the Pancreatic Endocrine Cells of the C57BL/6 Mouse

The regional distribution and relative frequency of the pancreatic endocrine cells in the C57BL/6 mouse were studied by immunohistochemical method using four types of specific mammalian antisera against insulin, glucagon, somatostatin and human pancreatic polypeptide (PP). The pancreas of mouse could be divided into three portions; pancreatic islets, pancreatic duct and exocrine portions, and pancreatic islets were further subdivided into three regions (central, mantle and peripheral regions) according to their located types of immunoreactive cells and pancreatic duct portions were also subdivided into two regions (epithelial and connective tissue regions). In the pancreatic islet portions, although some cells were also demonstrated in the mantle regions, most of insulin-immunoreactive cells were located in the central regions and they were randomly dispersed in the whole pancreatic islets. Glucagon-immunoreactive cells were detected in the mantle and peripheral regions. Their relative frequencies in the peripheral regions were somewhat numerous than those of the mantle regions. Somatostatin-immunoreactive cells were detected in the mantle and peripheral regions. However, no PP-immunoreactive cells were demonstrated in the pancreatic islets of C57BL/6 mouse. In the pancreatic duct portions, rare glucagon-immunoreactive cells were situated in the epithelial regions. Cell clusters that consisted of glucagon- or somatostatin- immunoreactive cells were found in some case of connective tissue regions of pancreatic ducts. However, insulin- and PP-immunoreactive cells were not detected in the epithelial nor connective tissue regions. In the exocrine portions, all four types of immunoreactive cells except for PP cells were demonstrated in the C57BL/6 mouse. However, no PP-immunoreactive cells were demonstrated. In conclusion, regional distribution of endocrine cells in the pancreas of C57BL/6 mouse was similar to that of mammals, especially other rodents except for topographically different distribution of endocrine cells compared to that of other rodents.

Immunohistochemical Study of the Pancreatic Endocrine Cells in the BALB/c mice: An Unique Distributional Pattern of Glucagon

The regional distribution and relative frequency of insulin-, glucagon-, somatostatin- and pancreatic polypeptide (PP)-producing endocrine cells in the pancreas of BALB/c mouse were investigated by immunohistochemical method. The pancreas of mice was divided into two portions; pancreatic islets and exocrine portions, and pancreatic islets were further subdivided into two regions (central and peripheral regions) and the relative frequency and regional distribution of immunoreactive cells against insulin, glucagon, somatostatin and PP antisera were monitored. In the pancreatic islet portions, insulin-immunoreactive cells were located in the central regions and they were randomly dispersed in the whole pancreatic islets in some case of the small islets. Quite different from those of other mammals, glucagon-immunoreactive cells were dispersed throughout central to peripheral regions in case of large islets and in the smaller ones, most of these cells were situated in the peripheral regions. Somatostatin-immunoreactive cells were detected in the peripheral regions with various frequencies. Although some cells were demonstrated in the central regions of pancreatic islets, most of PP-immunoreactive cells were located in the peripheral regions. In the exocrine portions, all four types of immunoreactive cells were demonstrated in the BALB/c mouse. Some peculiar distributional patterns of pancreatic endocrine cells were found in BALB/c mouse, especially in case of glucagon-immunoreactive cells.

Regional Distribution and Relative Frequency of Gastrointestinal Endocrine Cells in Large Intestines of C57BL/6 Mice

The regional distributions and relative frequencies of some gastrointestinal endocrine cells in the three portions (cecum, colon and rectum) of the large intestinal tract of C57BL/6 mice were examined with immunohistochemical method using 7 types of specific antisera against chromogranin A (CGA), serotonin, somatostatin, human pancreatic polypeptide (HPP), glucagon, gastrin and cholecyctokinin (CCK)-8. In this study, all 3 types of immunoreactive (IR) cells were identified. Most of these IR cells in the large intestinal portion were generally spherical or spindle in shape (open-typed cell) while cells with a round shape (close-typed cell) were found in the intestinal gland. Their relative frequencies varied according to each portion of the large intestinal tract. CGA-IR cells were found throughout the whole large intestinal tract but were most predominant in the colon. Serotonin-IR cells were detected throughout the whole large intestinal tract and showed highest frequency in the colon. Peculiarly, glucagon-IR cells were restricted to the colon with a low frequency. However, no somatostatin-, HPP-, gastrin- and CCK-8-IR cells were found in the large intestinal tract. In conclusion, some peculiar distributional patterns of large intestinal endocrine cells were identified in C57BL/6 mice.

Somatostatin (SRIF) like immunoreactivity in median eminence (ME) of female rat brain: evidence of compartmentalization in ME.

Somatostatin (SRIF) immunoreactivity was observed in rostrocaudal extent (Bregma levels-1.8 mm to -3.8 mm) of the median eminence (ME) in female rat brain using Avidin-Biotin Complex (ABC) method (Hsu et al, 1981). SRIF immunoreactivity (IR) was observed in entire-rostrocaudal extent of both internal (IZ) and external zone (EZ) of ME. Image analysis of SRIF stained sections showed that in rostral ME (Bregma -1.8 to -2.3 mm) dense immunoreactive nerve terminals were observed in EZ. In medial ME (Bregma -2.3 mm to 3.3 mm) SRIF-IR was low in IZ and dense in EZ. In this region dense immunoreactive nerve terminals were observed in lateral margin of EZ. In caudal ME (Bregma -3.3 mm to -3.8 mm) nerve terminals in lateral EZ and median IZ and EZ showed dense reactivity in nerve terminals. These results led us to hypothesize that each region-lateral IZ and EZ and medial IZ and EZ are independent functional units in ME. Six functionally independent compartments could be identified-Compartment I and III of IZ and IV in EZ (Lateral margins in ME), Compartment V (IZ) and Compartment VI (medial EZ).

Effect of Helicobacter pylori infection on antral gastrin and somatostatin cells and on serum gastrin concentrations

OBJECTIVES: Helicobacter pylori infection induces selective reduction of the number of antral D-cells and results in abnormal regulation of serum gastrin secretion. The purpose of this study was to investigate the relationship between H. pylori infection and the numbers of G-cells and D-cells. METHODS: The numbers of antral G-cells and D-cells, the ratio of G-cells to D-cells and fasting serum gastrin concentrations were compared between 37 patients with (29 with duodenal ulcers and 8 with gastric ulcers) and 33 without H. pylori infection (22 with duodenal ulcers and 11 with gastric ulcers). Serum gastrin concentrations were measured using the radioimmunoassay technique. Antral mucosal biopsy specimens were examined using immunohistochemical staining with antibodies specific for gastrin and somatostatin and the numbers of G-cells and D-cells per gastric gland were counted. RESULTS: Fasting serum gastrin concentrations were significantly higher in patients with H. pylori infection compared to patients without infection (80.3 +/- 23.5 vs 47.6 +/- 14.1 pg/ml, p 0.5). The number of D-cells was significantly lower in patients with H. pylori infection than in uninfected patients in both duodenal and gastric ulcer patients (1.3 +/- 0.4 vs 2.5 +/- 1.6, respectively, p < 0.001). The ratio of G-cells to D-cells was also significantly higher in infected patients compared with uninfected patients for both gastric and duodenal ulcers (5.7 +/- 2.7 vs 3.5 +/- 1.9, respectively, p < 0.001). CONCLUSIONS: These results strongly suggest that Helicobacter pylori infection induces reduction of the number of antral D-cells. The resulting relative hypofunction of the inhibitory action of D-cells against G-cells may be responsible for increased serum gastrin secretion.

Sistema hormona del crecimiento-efector y su rol en el crecimiento infantil / Growth-effector hormone system and it role in children growth

La consulta por retraso del crecimiento es muy frecuente en pediatría. En la última década se han efectuado importantes avances en la comprensión de los mecanismos hormonales que regulan el crecimiento infantil. Este artículo tiene por objeto hacer una actualización sobre el sistema hormona de crecimiento (GH) -efector. Se revisan los mecanismos de control hipotalámico de la secreción de GH (factor liberador de GH y somatotastina), secreción hipofisiaria de GH, la proteína ligadora de GH (GHBP), el receptor de GH y sus efectores periféricos (IGFs e IGFBPS). Se analizan las repercusiones clínicas de las alteraciones de cada uno de estos componentes, que pueden conducir a una falla en el crecimiento durante la infancia

Secreçäo de hormônio de crescimento e nutriçäo / Growth hormone secretion and nutrition

As açöes do hormônio de crescimento em promover o crescimento esquelético e no metabolismo säo indiretas e diretas, respectivamente. As açöes indiretas säo mediadas através das somatomedinas ou fatores de crescimento e as diretas säo predominantemente antagonistas às da insulina. A liberaçäo do hormônio de crescimento é determinada por um equilíbrio dinâmico de peptídios hipotalâmicos inibitórios e estimulatórios que säo a somatostatina e o hormônio liberador de hormônio do crescimento. A resposta hipotálamo-hipófise da liberaçäo do hormônio de crescimento pode ser influenciada pela idade, sexo, insulina, hormônios esteróides e da tireóide e o estado nutricional. Assim, há uma importante interrelaçäo entre as açöes do hormônio de crescimento, crescimento e estado nutricional

Respuesta al factor liberador en niños con deficiencia de hormona de crecimiento / Growth hormone response to releasing factor in growth hormone deficient children

El factor liberador de hormona de crecimiento (GRF) es un péptido de 44 aminoácidos producido en el hipotálamo, que estimula la secreción de hormona de crecimiento (GH) por la hipófisis. Este factor fue administrado a 21 niños prepuberales (12 varones y 9 mujeres) portadores de deficiencia de hormona de crecimiento. La edad cronológica promedio fue de 8,9 ñ 3,5 años, y su edad ósea de 5,6 ñ 2,6 años. El diagnóstico de deficiencia de GH se basó en una talla 2 DE bajo la media, velocidad de crecimiento inferior a 4,5 cm/año, respuesta inferior a 7 ng/ml a 2 diferentes pruebas de estímulo para GH, y ausencia de otras afecciones. La respuesta al estímulo con GRF fue definida como positiva cuando los niveles de GH aumentaron por sobre 4 veces al coeficiente de variación del radioinmunoensayo utilizado, lo que se registró en 13 de los 21 pacientes (62%). La respuesta máxima al GRF fue 17,2 ñ 10,8 ng/ml y se observó entre 5 y 30 min después de su administración. Los resultados positivos en 62% de los pacientes estudiados sugieren que sus defectos residen en el hipotálmo más que en la hipófisis. Estos niños se podrían beneficiar de un tratamiento a largo plazo con GRF

Inhibitory effect of calcitonin on growth hormone response to growth hormone releasing hormone in acromegaly

1. A neuroendocrine role for calcitonin (CT) has been suggested by the finding of CT receptors in the hypothalamus. We have recently shown that salmon calcitonin (sCT) inhibits growth hormone releasing hormone (GHRH)-induced GH secretion in msn by a mechanism apparently independent of changes in peripheral cortisol, glucose, calcium or parathyroid levels. 2. We have further investigated the inhibitory action of sCT on GH secretion by studying the effects of sCT (100 MRC units, im) or placebo on basal and GHRH (1-29) NH2 (50µg, iv) stimulated GH secretion in 6 acromemgalic patients with active disease. 3. Basal GH lelvels were not altered by sCT administration (placebo: 136 ñ 99 µg/1 vs sCT: 99 ñ 53 µg/1). However, the GH response to GHRH was decreased by sCT. The area under the curve was signficantly smaller when patients were treated with sCT compared to placebo controls (placebo: 77202 ñ 57036 vs sCT: 64828 ñ 51909 µg min-1 1-1; P < 0.01). No changes in glucose or calcium levels were observed. 4 These results demonstrate that sCT decresases GHRH-induced GH secretion in acromegalic patients. Although the mechanism of action of sCT on GH secretion is unknown, our results indicate that the inhibitory effect of this peptide on GH secretion is also observed in patients harboring pituitary adenomas

Dose-dependent effects of vasoactive intestinal polypeptide on somatostatin release from hypothalamic fragments in vitro

Vasoactive intestinal polypeptide (VIP) is present in high concentrations in the hypothalamus and appears to be involved in the modulation of growth hormone (GH) secretion. The effects of VIP on huypothalamic somatostatin (SMS) release are, however, controversial. To further elucidate the mechanism of action of this peptide on GH secretion we studied the effects of VIP on SMS secretion from incubated rat hypothalamic fragments in vitro. At 10**6 M, VIP induced a significant increase in basal SMS release (P<0.01), whereas at 10**-10 M it had an inhibitory effect. We suggest that the increase in GH after in vivo administration of VIP may be modulated, at least in part, by a direct effect of this peptide on SMS neurons, while the stimulatory effect of high doses of VIP on SMS release may represent a pharmacological interaction of this peptide with growth hormone releasing hormone, peptide histidine isoleucine, or glucagon receptors

Insulin secretion induced by allogeneic lymphocytis in geneticaly diabetic mice C57BL/KsJ mdb

Se estudió la secreción de insulina y somatostatina (SRIF) inducida por aloantígenos en el ratón genéticamente diabéticos de la cepa C57BL/KsJ mdb-mdb. Ratones diabéticos (db) inyectados con linfocitos alogeneicos (LA) no mostraron ningún incremento en la segunda fase de secreción estimulada por glucosa 27.5 mM y sólo levemente aumentaron su primera fase. Ratones normales inyectados con LA mostraron un incremento significativo en ambas fases de la secreción de insulina estimulada por glucosa 27.5 mM. La secreción de somatostatina de ratones normales o diabéticos inyectados con linfocitos alogeneicos no difirió de aquella obtenida cuando se inyectaron con linfocitos singeneicos. Linfocitos de ratones db inyectados en ratones alogeneicos causaron un incremento en la secreción de insulina que no difirió significativamente de la producida por la inyección de linfocitos alogeneicos de ratones no diabéticos. Linfocitos de ratón diabético inyectados en ratones singeneicos produjeron una secreción de insulina similar a la producida por la inyección de linfocitos de ratones singeneicos no diabéticos, y menor que la producida por la inyección de linfocitos alogeneicos. En resumen, los ratones db mostraron una respuesta hormonal deteriorada al estímulo antigénico, mientras que mantuvieron su acción aloantigénica