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P C Butler

Publications and source records attributed to P C Butler.

At least 37 records · Page 2Linked to original sources
PubMed1997

In humans at least 75% of insulin secretion arises from punctuated insulin secretory bursts.

Detection of insulin secretory bursts in peripheral blood is hampered by hepatic insulin extraction, dilution in the systemic insulin pool, and time-delayed damping of secretory burst amplitude. Previous studies in dogs in vivo and other experiments in vitro have shown that approximately 70% of all insulin is released within distinct insulin secretory bursts. To establish a method for detection and quantification of pulsatile insulin release in humans on the basis of peripheral insulin concentration measurements, we used a high-sensitivity, -specificity, and -precision insulin enzyme-linked immunosorbent assay (ELISA) and optimized an established deconvolution methodology to quantify the frequency, mass, and amplitude of insulin secretory bursts as well as to estimate the relative contribution of pulsatile insulin release to overall insulin secretion. By use of minutely sampled serum insulin concentrations measured by a highly sensitive insulin ELISA and insulin kinetics of 2.8 min (first half-life), 5.0 min (second half-life), and a fractional slow component of 0.28, the deconvolved insulin secretion rates in 20 healthy subjects during glucose infusion (4.5 mg.kg-1.min-1) could be resolved into a series (4.7 +/- 0.1 min/pulse) of approximately symmetric insulin secretory bursts with a mean mass of 87 +/- 12 pmol.l-1 pulse-1 and a mean amplitude (maximal release rate) of 35 +/- 4.7 pmol.l-1.min-1. The relative contribution of pulsatile to overall insulin secretion was 75 +/- 1.6% (range 59-85%). We conclude that in vivo insulin secretion in humans during nominal glucose stimulation consists of a series of punctuated insulin secretory bursts accounting for > or = 75% of total insulin secretion.

Activity Cycles↗
PubMed1996

Spontaneous diabetes mellitus in transgenic mice expressing human islet amyloid polypeptide.

The islet in non-insulin-dependent diabetes mellitus (NIDDM) is characterized by loss of beta cells and large local deposits of amyloid derived from the 37-amino acid protein, islet amyloid polypeptide (IAPP). We have hypothesized that IAPP amyloid forms intracellularly causing beta-cell destruction under conditions of high rates of expression. To test this we developed a homozygous transgenic mouse model with high rates of expression of human IAPP. Male transgenic mice spontaneously developed diabetes mellitus by 8 weeks of age, which was associated with selective beta-cell death and impaired insulin secretion. Small intra- and extracellular amorphous IAPP aggregates were present in islets of transgenic mice during the development of diabetes mellitus. However, IAPP derived amyloid deposits were found in only a minority of islets at approximately 20 weeks of age, notably after development of diabetes mellitus in male transgenic mice. Approximately 20% of female transgenic mice spontaneously developed diabetes mellitus at 30+ weeks of age, when beta-cell degeneration and both amorphous and amyloid deposits of IAPP were present. We conclude that overexpression of human IAPP causes beta-cell death, impaired insulin secretion, and diabetes mellitus. Large deposits of IAPP derived amyloid do not appear to be important in this cytotoxicity, but early, small amorphous intra- and extracellular aggregates of human IAPP were consistently present at the time of beta-cell death and therefore may be the most cytotoxic form of IAPP.

Aging↗
PubMed1996

Galanin microinjected into the medial preoptic nucleus facilitates female- and male-typical sexual behaviors in the female rat.

Galanin (GAL) microinjected within the sexually dimorphic medial preoptic nucleus (MPN) facilitates male-typical sexual behaviors in the male rat, a response that requires the presence of testosterone. As in the male, GAL-immunoreactive cells located within the MPN of the female also concentrate gonadal steroids and become less immunoreactive after gonadectomy. Thus, to investigate sexual behaviors in the female and to determine whether effects are comparable to those obtained in the male, GAL was microinjected unilaterally within the MPN of female rats. We report that GAL stimulated female-typical lordosis behavior after estrogen priming, and that the effect was not due to general arousal as measured by nonspecific locomotor activities. In a separate experiment, GAL microinjected within the MPN dose-responsively increased mount frequencies and decreased mount latencies in testosterone-primed females. A higher dose of testosterone was required in females for this stimulation of male-typical sexual behavior than required in a previous experiment in males.

Animals↗
PubMed1996

Effects of somatostatin on pulsatile insulin secretion: elective inhibition of insulin burst mass.

Although it is well known that somatostatin inhibits net insulin secretion, it is unknown whether this is achieved by regulation of the basal or pulsatile components of insulin secretion and, if the latter, whether this is through modulation of pulse mass or frequency. We addressed these questions with a canine model. Portal vein blood was sampled at 1-min intervals in five dogs for 60 min before (basal) and 90 min after ingestion of 30 g glucose on two different occasions, during a saline (SAL) or a somatostatin (SMS, 175 ng/min) infusion. Plasma glucose concentrations were similar during SAL and SMS. SMS had no effect on pulse frequency before (8.4 +/- 0.7 vs. 9.2 +/- 1.0 pulses/h, SMS vs. SAL, P = 0.54) or after glucose (13.3 +/- 1.1 vs. 11.6 +/- 0.9 pulses/h, SMS vs. SAL, P = 0.22). In contrast, SMS decreased insulin pulse mass in the postabsorptive (84 +/- 28 vs. 214 +/- 73 pmol/pulse, SMS vs. SAL, P < 0.05) and fed states (676 +/- 143 vs. 913 +/- 183 pmol/pulse, SMS vs. SAL, P < 0.05). In the postabsorptive state, SMS decreased insulin clearance by approximately 50% (0.32 +/- 0.04 vs. 0.60 +/- 0.09 l/min, P < 0.05), but after glucose ingestion, insulin clearance was comparable during SMS or SAL (0.72 +/- 0.04 vs. 0.80 +/- 0.08 l/min, P = 0.4). SMS appeared to alter insulin clearance through modulation of insulin pulse amplitude, because in the postabsorptive state clearance was closely correlated to the pulse amplitude (r = + 0.87, P < 0.0001). In conclusion, somatostatin regulates the rate of insulin secretion by selective inhibition of pulsatile insulin secretion. Regulation of secretory burst mass (and amplitude) may secondarily influence transhepatic and thus total body clearance of endogenously secreted insulin and thereby serve as a novel mechanism to dictate the systemic insulin concentration.

Administration, Oral↗
PubMed1996

Islet amyloid and islet amyloid polypeptide in cynomolgus macaques (Macaca fascicularis): an animal model of human non-insulin-dependent diabetes mellitus.

To further characterize spontaneous diabetes mellitus in cynomolgus macaques (Macaca fascicularis) as a model for human non-insulin-dependent diabetes mellitus (NIDDM), we evaluated the morphologic characteristics of the endocrine pancreas of 4 diabetic and 12 age-matched nondiabetic cynomolgus macaques. In addition, the cDNA-predicted amino acid sequence for islet amyloid polypeptide (IAPP) of this species was determined. Islet amyloid deposits exhibiting typical congophilia and green birefringence were found in 4/4 diabetic animals and in 8/12 nondiabetics. Islet amyloid deposits were significantly more extensive in the diabetic macaques (P = 0.001), in which they occupied a mean of 60% of the islet area. In contrast, in the nondiabetic group the maximum islet area occupied by amyloid was 24% (group mean = 6.8%), with four animals having no detectable islet amyloid. Amyloid deposits consistently showed immunoreactivity for IAPP but not for insulin. Comparisons between group means for diabetic versus nondiabetic macaques showed significantly greater islet area (P = 0.01, 85,390 versus 36,540 microns 2) and significantly greater islet area fraction (P = 0.02, 0.065 versus 0.032) for the diabetic group. The cDNA-predicted amino acid sequence for cynomolgus IAPP was identical to that previously reported for pig-tail macaques (M. nemestrina) and had 92%, 86%, and 84% amino acid sequence identity with human, domestic cat, and murine IAPPs, respectively. These findings support the use of cynomolgus macaques as an animal model of human NIDDM.

Amino Acid Sequence↗
PubMed1996

Diabetes mellitus in cystic fibrosis is characterized by islet amyloidosis.

A high proportion of patients with cystic fibrosis (CF) develop diabetes mellitus. In common with type II diabetes mellitus, diabetes mellitus in CF is characterized by a progressive decline in beta-cell function and an approximately 50% decline in beta-cell mass. It is not known whether islet amyloidosis (characteristic of type II diabetes mellitus) is present in diabetes mellitus complicating CF. To address this, pancreatic samples were obtained at autopsy from 9 control cases (without CF) and 41 cases of CF that were, in turn, subdivided into 13 nondiabetic, 12 borderline diabetic, and 16 diabetic cases based on clinical criteria. Islet amyloid was detected by light microscopy in 69% cases of CF with diabetes mellitus, 17% of cases with borderline diabetes mellitus, and none of the nondiabetic cases. Islet amyloid was not present in any of the control cases. Islet amyloidosis derived from islet amyloid polypeptide is a characteristic feature of diabetes mellitus in CF as well as type II diabetes mellitus.

Adolescent↗
PubMed1996

Comparison of the ability of bread versus bread plus meat to treat and prevent subsequent hypoglycemia in patients with insulin-dependent diabetes mellitus.

We sought to determine whether treatment of hypoglycemia with a snack containing both protein and carbohydrate results in more prolonged protection against subsequent hypoglycemia than ingestion of carbohydrate alone. We studied six insulin-dependent diabetic subjects on two occasions. On both occasions subjects received a variable overnight insulin infusion to achieve euglycemia followed by a constant insulin infusion (approximately 0.5 mU x kg(-1) x min(-1)) designed to produce hypoglycemia. When glucose reached 50 mg/dL, subjects were fed a snack consisting of either bread (approximately 85 kcal) or bread plus meat (approximately 205 kcal). Both contained 15 g of carbohydrate. The insulin infusion was continued for the next 3 h or until glucose again fell to 50 mg/dL. Although bread plus meat resulted in a more marked rise (P < 0.05) in glucagon than did bread alone, neither the post treatment peak glucose concentration (73 +/- 4 vs. 70 +/- 6 mg/dL) nor the subsequent rate of fall of glucose (0.42 +/- 0.10 us. -0.35 +/- 0.07 mg/dL/min) differed. The present study shows that the rate of redevelopment of hypoglycemia does not differ after eating bread or bread plus meat. Therefore treatment of hypoglycemia with a protein-enriched snack merely adds calories rather prolonged protection against subsequent hypoglycemia.

Adult↗
PubMed1996

Effects of glucose ingestion versus infusion on pulsatile insulin secretion. The incretin effect is achieved by amplification of insulin secretory burst mass.

In the present studies, we used a recently validated canine model to determine 1) if glucose ingestion stimulates insulin secretion by amplifying the pulsatile component of insulin release, and if so, 2) whether this effect is achieved preferentially through burst mass or frequency modulation, and 3) if the mechanism of incretin effect of insulin secretion is mediated via the pulsatile mode of secretion. We report that 30 g of glucose ingestion stimulates an approximately 550% increase in the overall rate of insulin secretion (1.8 +/- 0.2 to 11.6 +/- 1.5 pmol.kg-1.min-1), which is achieved via an approximately 400% increase in the mass of insulin secreted per burst (202 +/- 38 to 1,003 +/- 147 pmol/pulse, P < 0.001) and a approximately 40% increase in burst frequency (8.7 +/- 0.5 to 12.3 +/- 0.6 pulse/h, P < 0.001). Of the insulin secreted after glucose ingestion, 68% (+/-4) was released in discrete secretory bursts. Further analyses showed that the incretin effect of ingested (GPO) versus infused glucose (GIV) is achieved through regulation of pulsatile insulin secretion. Glucose ingestion led to an approximately 70% greater rate of insulin secretion than intravenous glucose delivery (10.0 +/- 1.6 vs. 5.9 +/- 0.9 pmol.kg-1.min-1, P < 0.005, GPO vs. GIV). This incretin effect was achieved by the specific mechanism of an approximately 70% greater pulse mass (930 +/- 196 vs. 558 +/- 97 pmol/pulse, P < 0.02, GPO vs. GIV) but with a comparable pulse frequency (13.1 +/- 0.9 vs. 12.0 +/- 0.5 pulses/h, P = 0.14, n = 9 dogs, GPO vs. GIV). We conclude that in vivo glucose regulates overall insulin secretion almost exclusively by amplification of the pulsatile mode of insulin secretion, and that the incretin effect is achieved by preferential enhancement of insulin secretory burst mass.

Animals↗
PubMed1996

Mechanisms of sulfonylurea's stimulation of insulin secretion in vivo: selective amplification of insulin secretory burst mass.

Although sulfonylureas enhance insulin secretion, it is unknown whether these hypoglycemic chemicals stimulate insulin secretion through the augmentation of the pulsatile or basal modes of insulin release. Enhanced pulsatile insulin could occur in turn through amplification of the burst mass or an increase in burst frequency. To address the mechanism of sulfonylurea action, we employed a recently validated canine model with a portal vein sampling catheter and flow probe to measure pulsatile insulin secretion in vivo directly in response to tolbutamide infusion or ingestion. After a 16-h fast, seven dogs were studied in the postabsorptive basal state and during a tolbutamide (0.2 mg/min) infusion when their plasma glucose concentrations were clamped at euglycemia. Insulin concentrations in the carotid artery (basal vs. tolbutamide, 85 +/- 12 vs. 325 +/- 66 pmol/l; P < 0.01) and portal vein (basal vs. tolbutamide, 345 +/- 55 vs. 1,288 +/- 230 pmol/l; P < 0.01) increased during tolbutamide infusion, but the portal vein plasma flow did not change. Increased plasma insulin concentrations were achieved by a fourfold increase in the total insulin secretion rate (2.3 +/- 0.2 to 9.4 +/- 1.9 pmol x kg(-1) x min(-1); basal vs. tolbutamide, P < 0.01). The augmented total insulin secretion was achieved mechanistically via a marked and selective increase in the insulin secretory burst mass (basal vs. tolbutamide, 266 +/- 64 vs. 817 +/- 144 pmol/pulse; P < 0.01), with no change in portal-vein insulin pulse frequency (basal vs. tolbutamide, 10.1 +/- 0.6 vs. 11.1 +/- 0.8 pulses/h; P = 0.3). Oral (250 mg) tolbutamide also magnified the endogenous insulin secretion rate by the preferential amplification of the secretory pulse mass (basal vs. tolbutamide, 167 +/- 37 vs. 362 +/- 50 pmol/pulse; P < 0.01). Neither the infusion nor the ingestion of tolbutamide changed the calculated clearance rates of endogenously secreted insulin. We conclude that sulfonylurea (tolbutamide) induced insulin secretion in vivo is achieved by the highly selective amplification of insulin secretory burst mass with no change in basal insulin release or the frequency of the beta-cell-network pacemaker.

Animals↗
PubMed1996

Treatment with growth hormone and dexamethasone in mice transgenic for human islet amyloid polypeptide causes islet amyloidosis and beta-cell dysfunction.

Islet amyloid derived from islet amyloid polypeptide (IAPP) is a well-recognized feature of type II diabetes. However, the mechanism of islet amyloidogenesis is unknown. In vitro studies suggest that amino acid residues 20-29 in human, but not mouse, IAPP confer amyloidogenicity consistent with the absence of spontaneous islet amyloidosis in mice. Several clinical and in vitro studies suggest that increased synthetic rates of IAPP predispose to IAPP-amyloidosis. In the present study, we sought to test the hypothesis that pharmacological induction of insulin resistance in a mouse transgenic (TG) for human IAPP would induce islet amyloid and beta-cell dysfunction. TG and non-transgenic (N-TG) control mice were treated with both rat growth hormone (12 micrograms/day) and dexamethasone (0.24 mg/day) (dex/GH) or received no treatment for 4 weeks, after which animals were killed to examine islet morphology. Treatment with dex/GH caused hyperglycemia (7.3 +/- 0.4 vs. 5.2 +/- 0.1 mmol/l, TG vs. N-TG, P < 0.001) associated with a decreased plasma insulin concentration (595 +/- 51 vs. 996 +/- 100 pmol/l, TG vs. N-TG, P < 0.05) in TG versus control mice. Islet amyloid was induced in treated TG mice but not in control mice. Islet amyloid was identified in both intra- and extracellular deposits, the former being associated with evidence of beta-cell degeneration. We conclude that dex/GH treatment in mice TG for human IAPP induces IAPP-derived islet amyloid, hyperglycemia, and islet dysfunction. The present model recapitulates the islet morphology and phenotype of type II diabetes.

Amyloid↗
PubMed1996

Measurement of insulin pulsatility by sampling directly from the portal vein: a surgical model for placement of long-term prehepatic vascular sampling catheters.

A practical and repeatable method for measurement of pulsatile insulin release in the dog was developed by direct, chronic cannulation of the portal vein cephalad to the pancrease and the entry point of the cranial pancreaticoduodenal vein, with subsequent exteriorization of the sampling catheter. Mixed breed male dogs of various body weights and ages underwent midline laparotomy for exposure of the portal vein system. After exposure the portal vein was dissected free and cannulated through a purse-string suture placed just caudad (approximately 1 cm) to the entry point of the cranial pancreaticoduodenal vein with a cuffed, medical grade, silastic catheter. The catheter was advanced cranial to a point just distal to the level of the liver and secured in place via the purse-string suture and a single stay suture. The catheter was then passed through the dorsolateral abdominal wall and routed subcutaneously to a point between the shoulder blades. After catheter plug attachment the catheter was tested for patency, flushed, heparin locked, then was secured to the subcutaneous tissue between the scapulas. The dorsal skin wound and abdominal incision were closed in a routine manner, and the dogs recovered from anesthesia. Catheter patency and function in all dogs were maintained for periods up to 4 weeks. No postoperative complications such as catheter tract infections occurred, maintenance was minimal, and all dogs were afforded complete freedom of movement and activity throughout the study, with no requirement for cumbersome jackets or wraps.

Animals↗
PubMed1995

Impact of sampling technique on appraisal of pulsatile insulin secretion by deconvolution and cluster analysis.

Little is known about the optimal experimental conditions for assessing pulsatile insulin secretion in vivo. To address this, we employed a recently validated canine model (n = 12) to determine the consequences of 1) sampling from the systemic circulation (SC) vs. the portal vein (PV), 2) sampling intensity and duration, and 3) deconvolution vs. cluster analysis on assessing pulsatile insulin secretion. PV vs. SC sampling resulted in a approximately 40% higher pulse frequency by deconvolution (9.0 +/- 0.5 vs. 6.6 +/- 0.9 pulses/h, P < 0.02) and cluster analysis (7.5 +/- 0.3 vs. 5.6 +/- 0.6 pulses/h, P < 0.01) due to a higher signal-to-noise ratio (19 +/- 4.8 PV vs. 12 +/- 1.8 SC). PV sampling also disclosed a higher calculated contribution of the pulsatile vs. nonpulsatile mode of delivery to total insulin secretion (57 +/- 4 vs. 28 +/- 5%, P < 0.001). Analysis of the relevance of sampling intensity revealed that 1-min data yielded a markedly higher estimate of pulse frequency with PV sampling than 2-min data (9.0 +/- 0.5 vs. 5.4 +/- 0.5, P < 0.02, deconvolution; 7.5 +/- 0.3 vs. 4.3 +/- 0.6 pulses/h, P < 0.001, cluster). Optimal sampling duration was shown to be 40 min or more. We conclude that the resolving power of the analytical tool, the anatomic site of blood withdrawal, the frequency of blood sampling, and the duration of the total observation interval all significantly influence estimated insulin secretory pulse frequency and the fraction of insulin secreted in pulses. With the assumption that PV 1-min insulin data constitute the "gold standard," our in vivo inferences of 7.5-9.0 insulin pulses/h closely recapitulate in vitro islet secretory activity.

Animals↗
PubMed1995

Islet amyloid polypeptide in pancreatic tissue of children with persistent hyperinsulinemic hypoglycemia caused by primary islet hyperplasia and nesidioblastosis.

Islet amyloid is a recognized characteristic finding in insulinoma and secondary islet hyperplasia resulting from severe insulin resistance. Little information is available about the presence of islet amyloid in primary islet hyperplasia (nesidioblastosis) of childhood. Here we report that islet amyloid was not present in 12 children with primary islet hyperplasia associated with hyperinsulinemic hypoglycemia.

Amyloid↗
PubMed1995

Human islet amyloid polypeptide expression in COS-1 cells. A model of intracellular amyloidogenesis.

Non-insulin-dependent diabetes mellitus is characterized by concurrent loss of beta-cells and deposition of islet amyloid derived from islet amyloid polypeptide (IAPP). We have previously demonstrated that IAPP-derived amyloid forms intracellularly in humans with chronic excess insulin expression (eg, insulinoma and insulin receptor antibody-induced insulin resistance). To determine whether overexpression of IAPP results in intracellular amyloid in mammalian cells, we transfected COS cells with vectors expressing amyloidogenic human IAPP or non-amyloidogenic rat IAPP. Transfected COS-1 cells secreted comparable amounts of human IAPP and rat IAPP (2.1 to 2.8 nmol/L/48 hours). After 96 hours, 90% of cells expressing human IAPP contained amyloid fibrils and were degenerating or dead, whereas cells transfected with rat IAPP lacked amyloid and were viable. Thus, overexpression of human IAPP can result in intracellular amyloid formation that is associated with cell death, suggesting that intracellular amyloid may play a role in beta-cell loss in non-insulin-dependent diabetes mellitus.

Amyloid↗
PubMed1994

Augmented effect of short-term pulsatile versus continuous insulin delivery on lipid metabolism but similar effect on whole-body glucose metabolism in obese subjects.

The present study was designed to examine the effect of pulsatile versus continuous insulin delivery on glucose and lipid metabolism in insulin-resistant subjects. Six obese women (body mass index, 40.0 +/- 2.8 kg/m2) underwent a euglycemic glucose clamp (plasma glucose, 90 mg/dL) twice. In random order, insulin was infused intravenously for 375 minutes either at a constant rate (0.4 mU/kg/min) or in a pulsatile manner (2.4 mU/kg/min for 2 minutes followed by an off interval of 10 minutes). Endogenous insulin release was suppressed by infusion of somatostatin (250 micrograms/h). Mean circulating insulin concentrations were similar during the two protocols (pulsatile v continuous infusion, 60 +/- 10 v 56 +/- 9 mU/L), but pulsatile infusion was accompanied by oscillations with an amplitude of 120 mU/L. After 6 hours of pulsatile versus continuous insulin, isotopically determined total glucose disposal (3-3H-glucose) and hepatic glucose production (HGP) were comparable (pulsatile v continuous, 2.80 +/- 0.56 v 2.82 +/- 0.51 and 0.37 +/- 0.14 v 0.32 +/- 0.17 mg/kg/min). However, the rate of glucose oxidation (indirect calorimetry) was augmented (P < .05), whereas lipid oxidation tended to be diminished (.10 > P > .05) following pulsatile infusion. In addition, blood glycerol was more suppressed with pulsatile (31 +/- 9 nmol/L) than with continuous infusion (36 +/- 10 nmol/L, P < .05), whereas blood lactate, alanine, and 3-hydroxybutyrate were similar in the two infusion protocols.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1994

Islet amyloid polypeptide in human insulinomas. Evidence for intracellular amyloidogenesis.

Amyloid deposits that characteristically form in the pancreatic islets of patients with non-insulin-dependent diabetes mellitus (NIDDM) and in insulinomas are both derived from islet amyloid polypeptide (IAPP). Evidence from previous studies has suggested that deposition of IAPP-derived amyloid is related to inherent amyloidogenic sequences present within normal human IAPP, together with an increased production and local concentration of IAPP. However, whether the aggregation of IAPP to form amyloid fibrils is primarily an intra- or extracellular event is not clear. To address this question, we studied 20 human insulinomas by light and electron microscopy. By light microscopy, amyloid deposits were demonstrated in 13 of 20 (65%) human insulinomas. Furthermore, evaluation of Congo red-stained tumor sections showed small, globular or irregular, congophilic amyloid deposits within the cytoplasm of many tumor cells in 10 of 13 (77%) amyloid-containing insulinomas. Dense, punctate areas of IAPP immunoreactivity within tumor cells corresponded with the congophilic intracellular deposits. Ubiquitin immunoreactivity also was observed as punctate intracellular labeling and within large extracellular amyloid deposits. Among the 10 insulinomas available for electron microscopic evaluation, pathological IAPP-immunoreactive (immunogold) deposits were found in 3 of 5 insulinomas in which amyloid was demonstrated by light microscopy and in none of 5 tumors found negative for amyloid by light microscopy. Morphology of IAPP-immunoreactive deposits varied from those with the classical distinct 7- to 10-nm diameter nonbranching fibrils to those with distinct but faint fibrillarity to those without discernable fibrils.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Microinjection of galanin into the medial preoptic nucleus facilitates copulatory behavior in the male rat.

The medial preoptic area (MPOA) is an important region for masculine sexual behavior. Because galanin (GAL) immunoreactive cells within the MPOA are affected by the gonadal steroid environment and GAL binding is apparent, GAL was microinjected site specifically in 0, 10, 50, 100, and 500 ng doses in order to determine effects on copulatory behavior. Unilateral microinjection of GAL within the medial preoptic nucleus facilitated copulatory behavior in a dose-responsive fashion, evidenced by an increase in the percentage of males that displayed sexual behaviors and a decrease in mount and intromission latencies. These effects required the presence of gonadal steroids, and were not due to general arousal as measured in open field testing. The techniques of survival analysis were used to display data and for statistical analysis of intromission and mount latencies; these approaches revealed significant effects that were not evident with more commonly used procedures. The results support the suggestion that sexually dimorphic galaninergic cell groups within the MPOA are involved in gonadal steroid-induced masculine sexual behavior.

Animals↗