Splenic Lobe Research Articles

An immunocytochemical study of the endocrine pancreas in three genera of lacertids

The comparative morphology of the endocrine pancreas was studied in 11 species of lacertids. Four major cell types were identified immunocytochemically in the endocrine pancreas: glucagon-immunoreactive A-cells, insulin-immunoreactive B-cells, somatostatin-(SRIF)-immunoreactive D-cells, and pancreatic polypeptide(PP)-immunoreactive F-cells. Different distributions of the four cell types were seen in the endocrine tissue within the exocrine parenchyma. F-cells were rare or absent in the splenic lobe and abundant in the duodenal lobe, in which they were usually widespread in the exocrine parenchyma and rarer in the islets. The other three cell types were always present in the islets. The central core consisted of B- and A-cells, with B-cells predominating. The peripheral mantle was formed by A-cells and less abundant D-cells. Rare D-cells were also found in the central core. D- and F-cells showed projections often closely associated with capillaries. The observed arrangements in islets and isolated cells may represent an endocrine network that, in addition to systemic actions, may regulate exocrine function in a paracrine fashion.

Intra-islet insulin permits glucose to directly suppress pancreatic A cell function.

Inhibition of pancreatic glucagon secretion during hyperglycemia could be mediated by (a) glucose, (b) insulin, (c) somatostatin, or (d) glucose in conjunction with insulin. To determine the role of these factors in the mediation of glucagon suppression, we injected alloxan while clamping the arterial supply of the pancreatic splenic lobe of dogs, thus inducing insulin deficiency localized to the ventral lobe and avoiding hyperglycemia. Ventral lobe insulin, glucagon, and somatostatin outputs were then measured in response to a stepped IV glucose infusion. In control dogs glucagon suppression occurred at a glucose level of 150 mg/dl and somatostatin output increased at glucose greater than 250 mg/dl. In alloxan-treated dogs glucagon output was not suppressed nor did somatostatin output increase. We concluded that insulin was required in the mediation of glucagon suppression and somatostatin stimulation. Subsequently, we infused insulin at high rates directly into the artery that supplied the beta cell-deficient lobe in six alloxan-treated dogs. Insulin infusion alone did not cause suppression of glucagon or stimulation of somatostatin; however, insulin repletion during glucose infusions did restore the ability of hyperglycemia to suppress glucagon and stimulate somatostatin. We conclude that intra-islet insulin permits glucose to suppress glucagon secretion and stimulate somatostatin during hyperglycemia.

AUTOMATED LARGE-SCALE ISOLATION, IN VITRO FUNCTION AND XENOTRANSPLANTATION OF PORCINE ISLETS OF LANGERHANS

To evaluate the potential of utilizing porcine islet tissue as an alternative to human islet tissue for transplantation, we developed a method for the isolation of large amounts of highly purified porcine islets, and assessed the in vitro and in vivo function of the isolated islets after 1, 4, and 7 days of culture. The pancreatic duct of the splenic lobe was cannulated and distended by injection of Hanks' balanced salt solution containing 1.5 mg/ml collagenase. The pancreas was then processed by a modification of the automated digestion-filtration method developed in this laboratory, and with purification accomplished by Euro-Ficoll gradients (dialyzed Ficoll in Eurocollins solution), consisting of two layers of 1.108 and 1.091 g/cm3 density, topped with a layer of HBSS. The postpurification yield was 5203 +/- 645 (mean +/- SEM) islets per gram of pancreas with a number of islet equivalents (IE) per gram pancreas (islet equivalence: 150-microns-sized islets) of 3551 +/- 305, and a volume of 6.27 +/- 1.7 mm3 islet tissue per gram of pancreas. The islet purity exceeded 90%. Overnight-cultured, perifused porcine islets released 53.1 +/- 8.2 pM insulin/200 IE at 3.3 mM glucose, and 114.9 +/- 25.4 pM insulin/200 IE at 16.7 mM glucose (P less than 0.001 vs. basal output). When theophylline was added, insulin secretion increased to 264.2 +/- 63.2 pM/200 IE (P less than 0.001 vs. basal secretion and P less than 0.005 vs. secretion at 16.7 mM glucose). After 4 days of culture, the islets still responded to secretagogues. The functional integrity of the isolated islets was confirmed by reversal of diabetes in aL3T4 antibody-treated C57B/B6 diabetic mice: normoglycemia was promptly restored by transplanting 1000 overnight- or 7-day-cultured (24 degrees C) islets under the kidney capsule. These results suggest that continued improvements of porcine islet isolation and culture could permit the use of porcine islets in immunoalteration and immunoisolation studies that may lead to eventual human transplantation.

Immunocytochemical study of the endocrine pancreas in some species ofChalcides

Abstract In the endocrine pancreas of eight species of Chalcides four types of endocrine cells (designated A, B, D, and PP or F) were revealed by immunocytochemical methods. A cells were immunoreactive to anti‐glucagon serum: B cells to anti‐insulin serum; D cells to anti‐somatostatin serum; PP cells to anti‐pancreatic polypeptide serum. In the splenic lobe, where endocrine cells are mainly concentrated and form large insular masses, A cells represent the most abundant type and PP cells are very rare or absent. In the ventral lobe, con taining small endocrine islets, all four endocrine types are present. However A, B, and D cells are preferentially located in the median region, while PP cells are numerous in the lateral region, where they appear isolated or associated in small groups scattered in the exocrine parenchyma. It was suggested that this regional distribution of the endocrine cell types reflects the different em bryonic origin of the two pancreatic lobes and/or different cell fun ctions.

Endocrine-nutrition interactions in birds

This review will discuss the uses of avian models, particularly the chicken, to examine nutrition-endocrine interactions. The chicken has been employed extensively to examine nutritional effects. The effects of fasting, protein deficiency and calcium deficiency on endocrine status have been the subject of intense investigation in young chicks and adult female chickens. The ratio of circulating concentrations of triiodothyronine (T3) and thyroxine (T4) is substantially changed by fasting or protein deficiency. Similarly, protein deficiency reduces circulating concentrations of insulin-like growth factor I (IGFI) while protein deficiency increases growth hormone (GH). Moreover, protein deficiency increases the sensitivity and responsiveness of adrenocortical cells. The chicken also as advantages for studying diabetes, endocrine pancreatic functioning due to the splenic lobe of the pancreas being predominantly endocrine in nature, and the cellular mechanism of GH on chicken adipose tissue. The adult female chicken with its high calcium requirement is a unique system for examining nutritional effects on reproduction.

Vagal afferent fibers almost exclusively innervate islets in the rat pancreas as demonstrated by anterograde tracing

Anterograde tracing from the nodose ganglion with wheat germ agglutinin-horseradish peroxidase conjugate (WGA-HRP) was utilized to investigate vagal afferent innervation of the rat pancreas. Labelled afferent fibers were consistently detected in islets in all animals. Only about 10% of islets were labelled even in best cases. In only 5 out of 16 rats, acini and excretory ducts received afferent innervation. Injections into the right nodose ganglion resulted in labelling preferentially within the splenic lobe, whereas injections into the left ganglion labelled fibers predominantly in the duodenal lobe. These results point to a non-random distribution of vagal afferent fibers within the pancreas, and suggest a role for these afferents in the regulation of endocrine pancreatic function.

Lobe-Specific Responses of Cultured Islet Cells of Canine Pancreas to Carbamylcholine, Glucose, and Pancreatic Polypeptide

Using cultured islet cells from both splenic lobe (SL) and uncinate process (UP) of the dog pancreas, we have measured responses of insulin, glucagon, and pancreatic polypeptide (PP) to glucose, carbamylcholine (carbachol), and exogenous PP. The results show that both insulin and PP cells of the two developmentally distinct lobes of the pancreas respond differentially to secretagogues. The results suggest that PP may play a role in regulation of islet cell secretion. Secretion of insulin by SL and UP cultures in response to 28 mM glucose in a 2h incubation was significantly greater, 2.9- (p less than 0.01) and 1.5-fold (p less than 0.01), respectively, than secretion by respective control cultures at 2.8 mM glucose. The difference in degree of stimulation between SL and UP was also significant (p less than 0.02). At 2.8 mM glucose, SL and UP cultures secreted 10% and 8.8%, respectively, of immunoreactive insulin (IRI) contents of the cultured cells (NS). Dose-response curves showed that for up to 8.5 mM glucose the degree of stimulation of SL was no greater than UP, but the UP response had nearly plateaued; whereas, the SL response continued to increase, such that SL was greater than UP at 16.7 mM glucose (p less than 0.01). Secretion of PP by SL and UP cultures in response to 5 microM carbachol and 2.8 mM glucose in a 2-h incubation was significantly greater, 2.2- (p less than 0.002) and 3.9-fold (p less than 0.002), respectively, than secretion by respective control cultures without carbachol. The difference in degree of stimulation between SL and UP was also significant (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro release of pancreatic hormones following 99% pancreatectomy in the chicken

In vitro assessment was made of the hormone-release capability of splenic pancreatic tissue 16 days after adult chickens had 99% of the pancreatic mass surgically removed. The objective of this study was to evaluate if the enlargement of the splenic lobe remnant after 99% pancreatectomy was attended by alterations in the responsivity of hormone release and, if so, were such changes reflective of all pancreatic hormones. After a 24-hr fast, splenic lobe tissue was obtained from young adult chickens on Postoperative Day 16, diced into 18–22-mg cubes, and incubated in vitro in media containing varying amounts of glucose with or without added somatostatin (SRIF). At 15-min intervals, the tissue cubes were transferred to fresh media and samples of each medium measured for insulin, glucagon, and APP. Viability of the tissue after 75 min was tested by tissue response to added 5 m M phenylalanine. The results obtained indicated that while total content of all four hormones (including SRIF) increased with tissue enlargement, the concentration of each decreased significantly except for SRIF, which remained at control levels. Further, the sensitivity of the B-cell in releasing insulin when confronted by a glucose challenge was not altered by previous pancreatectomy, while that of glucagon release from the A-cell was depressed. A-cell responsivity to SRIF does not appear to be adversely affected by previous 99% pancreatectomy. APP release was least affected by SRIF addition to the media, although depression by high glucose occurred. It is concluded that differential alterations occur in chicken pancreatic hormone-releasing cells as a result of 99% pancreatectomy. The efficacy in maintaining low, but still adequate, plasma I/G molar ratios (reported earlier) by the splenic remnant tissue either reflects a remarkable functional readjustment to surgical removal of 99% of the pancreatic mass in chickens or, alternatively, suggests the existence of extrapancreatic sources of insulin and glucagon, but not APP.

Reduction of glycemic potentiation. Sensitive indicator of beta-cell loss in partially pancreatectomized dogs.

To determine which test of islet function is the most sensitive indicator of subclinical beta-cell loss, we studied six conscious dogs before and 1 and 6 wk after removal of the splenic and uncinate lobes [64 +/- 2% pancreatectomy (PX)]. To assess hyperglycemic potentiation, acute insulin secretory responses (AIR) to 5 g i.v. arginine were measured at the fasting plasma glucose (FPG) level after PG was clamped at approximately 250 mg/dl and after PG was clamped at a maximally potentiating level of 550-650 mg/dl. FPG levels were unaffected by PX (112 +/- 4 mg/dl pre-PX vs. 115 +/- 5 mg/dl 6 wk after PX, P NS). Similarly, basal insulin levels remained constant after PX (11 +/- 2 microU/ml pre-PX vs. 11 +/- 1 microU/ml 6 wk after PX, P NS). The AIR to 300 mg/kg i.v. glucose decreased slightly from 42 +/- 9 microU/ml pre-PX to 32 +/- 5 microU/ml 6 wk after PX (P NS), and thus the beta-cell loss was underestimated. In contrast, insulin responses to arginine declined markedly after PX. The AIR to arginine obtained at FPG levels declined from 23 +/- 3 microU/ml pre-PX to 13 +/- 2 microU/ml 6 wk after PX (P = .04). The AIR to arginine obtained at PG levels of approximately 250 mg/dl declined even more, from a pre-PX value of 56 +/- 7 microU/ml to 21 +/- 4 microU/ml 6 wk after PX (P = .02).(ABSTRACT TRUNCATED AT 250 WORDS)

Pancreatic somatostatin, glucagon and insulin during post-hatch growth in the duck (Anas platyrhynchos).

Pancreatic somatostatin-like immunoreactivity (SLI), immunoreactive insulin (IRI) and glucagon-like immunoreactivity (GLI) were measured during growth in ducks. The content of each hormone increased progressively but at different rates in the dorsal, ventral and splenic lobes of the pancreas. In the almost fully grown duck, the splenic lobe contained 80 and 63% of the total content of GLI and SLI respectively but low levels of IRI (23%), which were highest in the dorsal lobe (53%). In contrast to the hormonal content, only total GLI concentrations increased during development, the SLI concentrations remaining stable and IRI concentrations declining during growth. Gel filtration of pancreatic extracts indicated that most of the SLI in the pancreas of young and adult birds was somatostatin-14, although somatostatin-28 was present in the ventral lobe of young birds and larger molecular forms were present in the ventral and dorsal lobes. These changes in pancreatic hormonal content and concentration are dissimilar to age-related changes in SLI, GLI and IRI previously observed in the plasma of ducks. Plasma levels of pancreatic hormones may thus be controlled by hormonal and/or neutral factors during post-hatch growth.

Calbindin D-27 kDa: preferential localization in non-B islet cells of the rat pancreas.

The presence and abundance of calbindin in rat pancreatic islet cells was assessed by immunohistochemistry of either whole islets or purified B and non-B islet cells, as well as by Western blotting of extracts derived from whole islets and purified B and non-B islet cells. Immunohistochemistry of pancreatic sections indicated a higher calbindin content in non-B cells, located at the periphery of the islets, than in the centrally located insulin-producing B cells. Comparable results were obtained in purified islet cells. Likewise, scanning densitometry of the Western blots indicated that, relative to cell volume, the single calbindin band (Mr 27 kDa) was 5-7 times higher in non-B than in B cells. In the splenic lobe of chick pancreas, however, the opposite situation prevailed. Thus, insulin-producing cells clustered in small roundish islets were more intensely labelled after exposure to anti-calbindin serum than non-B islet cells located in large and irregularly shaped islets. Nevertheless, even in the chick pancreas, non-B islet cells contained an appreciable amount of calbindin.

Evaluation of insulin secretion after pancreas autotransplantation by oral or intravenous glucose challenge.

Segmental pancreatic autotransplantation is accompanied by surgical alterations to the pancreas that may have consequences for carbohydrate metabolism. Four mongrel dogs were evaluated before operation and sequentially until 40 weeks after total pancreatectomy and autotransplantation of the splenic lobe of the pancreas with bolus intravenous and oral administration. Intravenous glucose tolerance test (IVGTT) (0.5 g/kg) revealed maintenance of fasting euglycemia for as long as 40 weeks after operation. Peak glucose and integrated glucose values did not show significant changes as a result of autotransplantation. Following transplantation, a delayed peak insulin response was seen; however, basal, peak, and integrated insulin values were largely unaltered. Only K values, a measure of glucose disposal, showed severe alterations (2.44 +/- 0.21 before operation to 1.24 +/- 0.30 at 40 weeks after operation). Oral glucose tolerance tests (OGTT) (2.0 g/kg) demonstrated an increased peak hyperglycemic response after autotransplantation with increased integrated glucose responses. Insulin levels remained at those levels seen before operation, and glucose-dependent insulinotropic polypeptide (GIP) responses were unchanged during the OGTT as late as 20 weeks after operation. In conclusion, pancreas autotransplantation after total pancreatectomy results in significant metabolic alterations that the IVGTT fails to detect with absolute glucose or insulin levels. However, K values are significantly lowered, which indicates alterations in cellular glucose transport. The OGTT demonstrates hyperglycemia without increased insulin or GIP levels, which suggests an altered beta cell response to the enteric stimulus of insulin release. These changes are nonetheless well tolerated by animals that have remained clinically healthy and euglycemic in the basal state.

Effectiveness of somatostatin in regulating pancreatic splenic lobe hormone secretion following 99% pancreatectomy in adult chickens

In vivo studies were carried out in adult chickens in an attempt to evaluate the effectiveness of somatostatin (SRIF) in regulating hormone secretion from the splenic pancreatic lobe after 99% of the pancreatic mass was surgically ablated. Sixteen days after either sham operation or 99% pancreatectomy, birds were infused iv with SRIF (420 ng/min) alone and then glucose (59 mg/Kg/min) was superimposed on the infusate, or birds were infused iv with glucose alone and then SRIF was superimposed on the infusate. Serial blood samples were taken during the 16-day postoperative period and also at regular intervals during the 75-min observation period. Plasma was analyzed for glucose, insulin (IRI), glucagon (IRG), pancreatic polypeptide (IRAPP), and somatostatin (IRSRIF). Careful standardization of the SRIF radioimmunoassay, as well as analysis of the molecular form of circulating SRIF, indicated that “true” SRIF levels were being estimated in plasma of both groups of chickens. Normal-fed chickens have plasma SRIF levels of 1.12 ± 0.07 ng/ml which increases 16 days after 99% pancreatectomy to 2.39 ± 0.15 ng/ml plasma. The latter decreases by 55% with an overnight fast. Glucose infusion, superimposed upon a preexisting SRIF infusion in adult chickens, did not evoke an IRI response in the 99% depancreatized birds equal to that observed in sham-op controls. Although a full SRIF dose-response curve was not generated, the glucose data strongly suggest a reduced sensitivity of insulin-secreting cells to SRIF in pancreoprivic birds. Both bird groups were equally—and markedly—sensitive to the IRG-depressant effects of SRIF; in contrast, the depancreatized chickens were significantly more resistant to the APP-inhibitory effects of SRIF when compared to the sham-op control birds. Thus, 16 days after partial pancreatectomy, the hormone-release mechanisms appeared altered for IRI and IRAPP in response to SRIF. Data obtained when glucose infusions preceded SRIF infusions indicated that A-cell release of glucagon was much more sensitive to glucose (as a depression) in the partially depancreatized birds than in control birds. These same birds were significantly less responsive to the glucose-depressant effect on plasma APP levels. Thus, it appears that 99% pancreatectomy increases the sensitivity of the SRIF, IRI, and IRG release mechanisms in response to glucose 16 days after surgery. The insulin-to-glucagon (I/G) molar ratios indicative of metabolic anabolism can still be achieved by nutrients 16 days after partial pancreatectomy. It is suggested that SRIF is intimately involved in the “fine tuning” of the I/G molar ratio in 99% depancreatized chickens. Whether the sensitivity alterations observed herein are reflective of receptor or postreceptor events, and whether these events take place within the splenic lobe remnant or at extrapancreatic sites, are yet to be elucidated.

The role of the splenic pancreatic lobe in regulating metabolic normalcy following 99% pancreatectomy in chickens

The functional competency of the splenic pancreatic lobe of adult chickens was evaluated by studying plasma and tissue levels of insulin (IRI), glucagon (IRG), somatostatin (IRSRIF), and avian pancreatic polypeptide (IRAPP) for 16 days following surgical removal of 99% of the pancreas. The rationale underlying this approach was to assess whether the splenic remnant tissue after 99% pancreatectomy was capable of maintaining apparent metabolic normalcy as has been suggested in the literature. Partial (99%) pancreatectomy resulted in almost immediate enlargement of the splenic remnant, immediate decreases in both plasma IRI and IRAPP, both of which subsequently reattained normal levels (IRI in 4 days and IRAPP in 16 days). Hyperinsulinemia persisted from Days 4–7 and then returned to normal the remaining 9 days. Plasma IRG levels increased markedly and progressively for the entire 16-day observation period. Plasma I/G molar ratios indicated a strong catabolic trend in the 99% depancreatized group approaching values of 0.4 by 4 hr postop, returning to normal by Day 5, only to decrease progressively again into another sustained catabolic mode of 0.8 or less for the additional 11 days. Splenic lobe hormone (total) content of IRI, IRG, and IRAPP increased significantly throughout the 16-day observation period; however, parenchymal enlargement of nonendocrine lobe tissue was so great that actual concentrations of IRI and IRG decreased significantly while IRAPP concentration appeared to remain constant at control levels. IRSRIF levels were very sensitive both to pancreatectomy (increasing 140% 16 days later) and to fasting (decreasing 52% after 48 hr). IRG levels increase with fasting and with the exception of IRAPP, pancreatectomy appeared to increase the “sensitivity” of the splenic remnant in responding to the fasting stimulus. The results suggest that very rapid enlargement of the remnant splenic lobe following 99% pancreatectomy is probably adequate to maintain an apparent metabolic normalcy in adult chickens. The depancreatized animal enters a strongly catabolic mode, due mainly to hyperglucagonemia, even though food intake is normal and body weight is constant (though at subcontrol levels) after 16 days. There is no evidence to support the suggestion that SRIF stimulates glucagon release.

Immunocytochemical studies on the development of the pancreatic islet cells in the domestic fowl.

The four main types of pancreatic endocrine cells in the developing chick embryo were studied by light microscopic immunocytochemistry to describe their time of appearance, localization, and changes in the distribution during development in connection with the formation of pancreatic lobes. A cells first appeared at day 3 of incubation in the dorsal pancreatic bud, and increased in number thereafter to form the alpha islets. The alpha islets became huge and complicatedly diverged like those in the adult at day 11, but remained restricted to the third and splenic lobes derived from the dorsal pancreatic bud. B cells first appeared at day 4 of incubation in distinct beta islets in the dorsal pancreatic bud, but only a few of them showed the intense immunoreaction to anti-insulin serum at this stage. At day 6, most of B cells constituting beta islets in the dorsal primary lobe became immunopositive to anti-insulin serum. At day 11, beta islets spread into the dorsal and ventral lobes derived from right and left ventral pancreatic buds. D cells appeared first in the dorsal pancreatic bud at day 4 and joined the alpha islets at day 5. At day 11, D cells joined the beta islets and appeared in the dorsal and ventral lobes as did B cells. APP cells first appeared at day 9 in the exocrine portion of four lobes and remained restricted to the exocrine pancreas independently from pancreatic islets.

The first appearance of endocrine cells in the splenic lobe of the embryonic chick pancreas.

In seeking a source of a pure population of a single type of endocrine cell, the splenic lobe of the chick pancreas was investigated. This was because, in adult life, this lobe contains an abundance of glucagon cells and only a few endocrine cells of other types. The presence of cells containing insulin, glucagon, somatostatin, and pancreatic polypeptide was sought by immunocytochemical means in splenic lobes of normal chicks of 6, 7, and 8 days incubation as well as in splenic lobes which had been removed from donors of the same ages and cultured in isolation from the rest of the pancreas as chorioallantoic grafts. Insulin and glucagon cells were present in all specimens. Somatostatin cells were found in all splenic lobes except one from a normal 6-day embryo. Avian pancreatic polypeptide (APP)-immunoreactive cells were detected in all grafts from donors of 6 or more days incubation and, in normal splenic lobes, were first found at 7 days of incubation. In all grafted and normal splenic lobes older than 7 days on original isolation, glucagon- and APP-immunoreactivities were occasionally present in the same cells. Thus, although the splenic lobe cannot be used as a pure endocrine cell source, this study has demonstrated APP immunoreactivity in the chick pancreas at an earlier stage than has previously been reported, and has also revealed "double staining" of some pancreatic endocrine cells with antisera raised to glucagon and APP.

Somatostatin-like immunoreactivity (SLI) in pancreatic and intestinal tissues of the duck. A possible origin for the portal circulating SLI.

Substances with Somatostatin-Like Immunoreactivity (SLI) were extracted using 2 N acetic acid, from the three pancreatic lobes and the intestine of the duck. The concentration of SLI was found to be very high in the pancreas (4.2 micrograms/g wet weight), the splenic lobe containing 80% of pancreatic SLI compared with 10% for the dorsal and 10% for the ventral lobes. SLI was equally distributed between duodenum, jejunum and ileum and between their mucosal and muscular layers. Chromatography of pancreatic extracts, using a Sephadex G-25 column, showed mainly the tetradecapeptide form (somatostatin-14, S-14) with a small amount of big somatostatin. Chromatography of intestinal extracts revealed three peaks with SLI: big somatostatin, somatostatin-28 (S-28) and S-14. The substance represented by the predominant peak was co-eluted with that of synthetic S-28. In normal ducks, portal plasma SLI corresponded to big somatostatin S-28 and S-14. After total pancreatectomy the S-14 form disappeared from portal plasma, whereas, when the intestinal blood vessels were ligatured, the S-28 form disappeared. We therefore hypothesize that in portal blood, S-14 has a mainly pancreatic origin, and S-28 a mainly intestinal origin.

Regional distribution of pancreatic polypeptide and other hormones in chicken pancreas: Reciprocal relationship between pancreatic polypeptide and glucagon

Tissue extracts of discrete lobes of chicken pancreas were assayed for pancreatic polypeptide (PP), glucagon, somatostatin (SRIF), and insulin by radioimmunoassay. Concentrations of all pancreatic hormones except PP were highest in the splenic lobe. PP concentration was greatest in the inferior portions of the three major lobes. There is a reciprocal relationship between PP and glucagon concentration in chicken pancreas. The results with extracts were substantiated by cell frequency measurements using immunocytochemical methods.

Immunocytochemical localization of the pancreatic islet cells in the Japanese quail, Coturnix coturnix japonica.

The endocrine pancreas of the Japanese quail (Coturnix coturnix japonica) was immunocyto-chemically studied on the distribution and cellular composition of the islets and the fine structure of islet cells. The pancreatic islets of the quail are divided into alpha, beta and mixed type islets on the ground of the cellular composition. The alpha islets are generally composed of A and D cells and restricted to the third and splenic lobes, whereas the beta islets are generally composed of B and D cells and distributed throughout the pancreas. Mixed type islets containing A, B and D cells are restricted to the third and splenic lobes. A cells contain spherical granules immunopositive to anti-glucagon and C-terminal specific anti-glicentin sera. B cells contain polymorphic granules immunopositive to anti-insulin and anti-duck C-peptide sera. D cells contain spherical granules immunopositive to anti-somatostatin serum. Mixed type islets are supposed to be formed by the mingling of A cells into beta islets in the splenic and third lobes. The beta islets composed solely of B cells are conspicuously small, scattered throughout the pancreas and seemed to be the remnants of immature beta islets observed during the development.

Pancreatic hormones, insulin/glucagon molar ratios, and somatostatin as determinants of avian carbohydrate metabolism.

The endocrine pancreas of birds contains cell populations similar, if not identical, to those found in mammalian pancreata, although the topographical distributions of these cell types differ to some extent. Insulin-secreting (B) cells, glucagon-secreting (A) cells, somatostatin-secreting (D) cells, and pancreatic polypeptide-secreting (PP or F) cells are distributed unequally among the four pancreatic lobes, with most of the A cells located in the third and splenic lobes and PP cells residing in both islet tissue and in acinar tissue. Glucagon appears to be a (the?) major pancreatic hormone involved in metabolic glucoregulation in birds. Yet the essentiality of insulin for this regulatory purpose also has been established. As a result, current thought is directed toward the molar ratio of insulin to glucagon (I/G) as a dominant force in homeostasis rather than toward either of the two hormones separately. Molar I/G ratios have been useful in mammals in studying the needs of the organism to produce glucose to meet a metabolic crisis/need and, when compared with that found in normal Aves, a value of 1.8-2.2 has been established. Such a molar ratio is indicative of a catabolic recovery of nutrients in mammals, suggesting that birds normally are in a catabolic mode (like diabetic, starving, or exercising mammals). Somatostatin (SRIF) is known to inhibit the release of all pancreatic hormones but has a greater inhibitory action on glucagon secretion than it does on any of the other peptides. (It has least effect on APP).(ABSTRACT TRUNCATED AT 250 WORDS)