Development of hypoglycemia and hyperglycemia as a function of number of trials in insulin conditioning

A neutral environment paired with insulin injections can develop the capacity to elicit glycemic changes. However, both conditioned hypoglycemia and conditioned hyperglycemia have been reported under apparently similar circumstances. The present study examined conditioned glycemic changes as a function of the number of conditioning trials and the novelty of the conditioning environment. Adult, male Wistar rats were injected with either insulin or physiological saline every second day, in either a novel or a familiar environment. On the test day, all rats were injected with saline and blood was collected 20 minutes later for determination of glucose levels. In rats given insulin in the novel environment, conditioned hypoglycemia was observed after two trials but was replaced by conditioned hyperglycemia after five trials. No conditioning at all occurred in the familiar environment. The two conditioned responses observed were interpreted as reflecting two unconditioned responses brought about by insulin--a hypoglycemic response to the central detection of insulin, and a hyperglycemic response to the detection of (insulin-induced) hypoglycemia. Taken in conjunction with previous experiments in which both conditioned response patterns have occurred, the present results suggest that the homeostatic response of hyperglycemia can become strong enough to overcome the initial conditioned response of hypoglycemia, but that its establishment depends on the use of a novel conditioned stimulus and a larger number of conditioning trials.     

Semisynthetic human insulin and purified pork insulin do not differ in their biological potency

Summary The biological potency of semisynthetic human insulin (Actrapid HM, Novo) and purified pork insulin (Actrapid MC, Novo) was assessed in normal and diabetic subjects. The blood glucose lowering effect and the related counter-regulatory response were initially tested in six healthy subjects who received an i.v. injection of 0.15 U/kg body weight of either insulin preparation. The attained insulin levels were very similar (peak at 15 min: HM 139±7, MC 129±7 µU/ml), as well as the resulting blood glucose curves. A prolonged suppression of C-peptide values was observed after injecting both preparations. The evoked counter-regulatory response [glucagon, growth hormone (GH), cortisol and catecholamines] showed minimal differences. Prolactin secretion was almost identical after HM and MC injection. A glucose clamp study was subsequently performed in six insulin-dependent diabetic (IDD) patients. Blood glucose levels were maintained at 80 mg/dl by the artificial pancreas during a 180 min infusion of MC or HM insulin (30 mU/kg/h). The amounts of dextrose infused during the last 60 min of the study were not significantly different (121±14 vs 137±11 mg/kg/h for MC and HM, respectively). It is clear from our results that at the dose levels used in this study, the biological potency of i.v. injected HM is very similar to that of MC.Abbreviations AUC area under the concentration: time curve - EDTA ethylene diamino tetraacetic acid - EGTA ethylene glycol tetraacetic acid - GCIIS glucose-controlled insulin infusion system - GH growth hormone - HM human semisynthetic insulin - IDD insulin-dependent diabetes - MBG mean blood glucose - MC monocomponent, highly purified pork insulin Supported by Landesversicherungsanstalt Württemberg and Dotation Herbert Weishaupt e.V.Fellow of the Deutscher Akademischer Austauschdienst 1982–1984Fellow of the Deutscher Akademischer Austauschdienst 1980–1982     

Association of a type 2 diabetes genetic risk score with insulin secretion modulated by insulin sensitivity among Chinese Hans

Type 2 diabetes (T2D) is characterized by insulin resistance and impaired insulin secretion. The present study aimed to identify the influence of insulin sensitivity on the genetic risk of impaired insulin secretion among a Chinese Han population. For 3229 controls and 1994 treatment‐naïve T2D, single nucleotide polymorphisms (SNPs) from 24 T2D‐related genomic loci were genotyped and a genetic risk score (GRS) was constructed. Results showed that GRS was associated with insulin secretion and disposition indices in both controls and treatment‐naïve T2Ds. Upon stratifying the participants into tertiles by the Matsuda index, we observed an inhibitory relationship between the GRS and insulin secretion in low insulin sensitive but not in high insulin sensitive controls and treatment‐naïve T2Ds. Moreover, low insulin sensitive individuals exhibited more severe impairment in insulin secretion and beta cell response to insulin sensitivity with an increase in risk alleles. Our findings identified that the association of GRS with insulin secretion was strongly modulated by insulin sensitivity in both controls and T2Ds of Chinese Han. It indicates that insulin sensitization should be emphasized in prevention and treatment of T2D for beta cell protection.     

Effect of the light-dark cycle on neuroendocrine and behavioral responses to scheduled feeding.

Rats, nocturnal animals, adapt both behaviorally and physiologically to a restricted feeding schedule. Such adaptations occur faster and more efficiently during the dark portion of a light-dark cycle as indicated by measurements of latency to eat, amount of food consumed, body weight, and insulin levels.     

Primary systemic allergy to human insulin: recurrence of generalized urticaria after successful desensitization

Primary systemic allergy to human insulin is rare. We report a case of recurrent immediate local reactions followed eventually by generalized urticaria to recombinant human insulin (Humulin) in an insulin-dependent diabetic. Skin test to Humulin R was positive, and the patient was successfully desensitized using a modified rapid desensitization protocol. Two weeks later, he had another episode of generalized urticaria after Humulin R injection. His treatment was resumed at a lower dose, and within a week he was able to tolerate his usual regimen of insulin. To our knowledge, this is the first report of a recurrence of systemic reaction after successful desensitization.     

Metformin during pregnancy reduces insulin, insulin resistance, insulin secretion, weight, testosterone and development of gestational diabetes: prospective longitudinal assessment of women with polycystic ovary syndrome from preconception throughout pregnancy

BACKGROUND: In a prospective observational study of 42 pregnancies in 39 Caucasian women (age 30 +/- 4 years) with polycystic ovary syndrome (PCOS), we examined effects of metformin on maternal insulin, insulin resistance (IR), insulin secretion (IS), weight gain, development of gestational diabetes (GD), testosterone and plasminogen activator inhibitor activity. We assessed the hypothesis that diet-metformin (MET) lessens the physiological gestational increase in IR and reduces gestational weight gain, thus reducing GD. METHODS: Preconception, in an out-patient clinical research centre, MET 1.5 (eight pregnancies) to 2.55 g/day (34 pregnancies) was started. Women with body mass index <25 or >or=25 kg/m(2) were given a 2000 or 1500 calorie/day, high-protein (26% of calories), low-carbohydrate (44%) diet. Calorie restrictions were dropped after conception. RESULTS: On MET, GD developed in three out of 42 pregnancies (7.1%). Median entry weight (94.5 kg) fell to 82.7 on MET at the last preconception visit (P = 0.0001), fell further to 81.6 during the first trimester, was 83.6 in the second trimester, and 89.1 kg in the third trimester. Median weight gain during pregnancy was 3.5 kg. The median percentage reduction in serum insulin was 40% on MET at the last preconception visit; insulin did not increase in the first or second trimesters (P > 0.05), and rose 10% in the third trimester. The median percentage reduction in HOMA IR was 46% on MET at the last preconception visit; IR did not increase (P > 0.05) in the first, second or third trimesters. HOMA insulin secretion fell 45% on MET at the last preconception visit, did not increase in the first trimester, rose 24% in the second trimester, and rose 109% in the third trimester. Testosterone fell 30% on MET at the last preconception visit (P = 0.01) and then rose 74, 61 and 95% during trimesters 1, 2 and 3; median testosterone during the third trimester did not differ from pre-treatment levels. CONCLUSIONS: By reducing preconception weight, insulin, IR, insulin secretion and testosterone, and by maintaining these insulin-sensitizing effects throughout pregnancy, MET-diet reduces the likelihood of developing GD, and prevents androgen excess for the fetus.     

GGPPS‐mediated Rab27A geranylgeranylation regulates β cell dysfunction during type 2 diabetes development by affecting insulin granule docked pool formation

Loss of first‐phase insulin secretion associated with β cell dysfunction is an independent predictor of type 2 diabetes mellitus (T2DM) onset. Here we found that a critical enzyme involved in protein prenylation, geranylgeranyl pyrophosphate synthase (GGPPS), is required to maintain first‐phase insulin secretion. GGPPS shows a biphasic expression pattern in islets of db/db mice during the progression of T2DM: GGPPS is increased during the insulin compensatory period, followed by a decrease during β cell dysfunction. Ggpps deletion in β cells results in typical T2DM β cell dysfunction, with blunted glucose‐stimulated insulin secretion and consequent insulin secretion insufficiency. However, the number and size of islets and insulin biosynthesis are unaltered. Transmission electron microscopy shows a reduced number of insulin granules adjacent to the cellular membrane, suggesting a defect in docked granule pool formation, while the reserve pool is unaffected. Ggpps ablation depletes GGPP and impairs Rab27A geranylgeranylation, which is responsible for the docked pool deficiency in Ggpps‐null mice. Moreover, GGPPS re‐expression or GGPP administration restore glucose‐stimulated insulin secretion in Ggpps‐null islets. These results suggest that GGPPS‐controlled protein geranylgeranylation, which regulates formation of the insulin granule docked pool, is critical for β cell function and insulin release during the development of T2DM. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Adiposity signaling and meal size control

Signaling from energy stores provides feedback on overall nutrient availability to influence food intake. Beginning with seminal studies by Woods and colleagues identifying insulin as an adiposity signal, it has become clear that such factors affect food intake by modulating the efficacy of within meal feedback satiety signals. More recent work with leptin has revealed actions of the hormone in modulating the efficacy of multiple gut feedback signals, identified the dorsal hindbrain as a site of signal integration and suggested both local and descending hypothalamic to hindbrain actions in mediating these effects. The original work by Woods and colleagues provided the necessary experimental paradigms for these advances.     

Importance of early postprandial insulin delivery in insulin-dependent diabetics

Summary In nine insulin-dependent diabetics postprandial glucose control under closed loop insulin infusion by an artificial endocrine pancreas was compared with that obtained under open loop infusion employing identical infusion profiles which were advanced 20 min by time in the case of open loop infusion. The earlier increase of insulin infusion rates in the latter case resulted in lower postprandial glucose concentrations during the first 90 min after meal intake. Incremental areas under the blood glucose curves during this time were significantly lower when insulin infusion rates rose earlier (4.5×10³±0.5×10³ vs 2.1×10³±0.6×10³ mg/dl×min;p<0.02). Insulin was administered at maximum rates 45–50 min after the start of the meal during closed loop infusion (196±38 mU/min) and 25–30 min after the meal during open loop infusion (192±35 mU/min). Correspondingly, mean free insulin concentrations which are available from six patients rose to 135±47 (40 min) or 141±50 µU/ml (20 min). Glucagon levels did not differ between both parts of the study. It is concluded that increases of post-prandial insulin infusion rates occurring earlier than increases of blood glucose levels are important for optimizing glucose profiles and possibly reflect physiologic conditions.Supported by Landesversicherungsanstalt Württemberg and Dotation Herbert Weishaupt e.V.Fellow of the Deutsche Akademische Austauschdienst 1981/82     

Role of increased insulin demand in the adaptation of the endocrine pancreas to pregnancy

Nieuwenhuizen, A. G., Schuiling, G. A., Moes, H. & Koiter, T. R. 1997. Role of increased insulin demand in the adaptation of the endocrine pancreas to pregnancy. Acta Physiol Scand 159 , 303–312. Received 8 July 1996, accepted 24 October 1996. ISSN 0001–6772. Department of Obstetrics and Gynaecology, University of Groningen, Groningen, the Netherlands. During gestation the demand for insulin increases due to a decrease in insulin sensitivity of the maternal tissues. Simultaneously, pancreatic islet-cell proliferation, as well as insulin production and secretion increase. Both phenomena appear to be caused by the actions of pregnancy hormones. We studied the relationship between the two phenomena by investigating whether the supply of exogenous insulin affects the secretion of pregnancy hormones and islet function during gestation. For that purpose rats were treated with high doses of insulin (4.8 IU day^?1 by sub-cutaneous osmotic mini pumps) so that the endogenous demand for insulin was fully satisfied from day 8–14 of gestation. Euglycaemia (5.0 mm ) was maintained by intra venous infusion of glucose. The treatment suppressed insulin synthesis, as measured by in situ hybridization, in both pregnant and cyclic rats. In addition, in pregnant rats the increments in insulin secretion and in islet-cell proliferation were partly prevented. Furthermore, the data also suggest that in pregnant rats the treatment partly prevented the decrease in insulin sensitivity. Finally, the treatment did not affect the plasma concentrations of progesterone, prolactin and placental lactogen, but prevented the rise in growth hormone concentrations in pregnant rats. The present data suggest that, next to direct effects of pregnancy hormones and growth hormone on the pancreatic islets, a decreased insulin sensitivity in the maternal tissues, induced by actions of the same hormones, is involved in the regulation of islet function during gestation.     

On high-frequency insulin oscillations

Insulin is released in a pulsatile manner, which results in oscillatory concentrations in blood. The oscillatory secretion improves release control and enhances the hormonal action. Insulin oscillates with a slow ultradian periodicity (∼140 min) and a high-frequency periodicity (∼6-10 min). Only the latter is reviewed in this article. At least 75% of the insulin secretion is released in a pulsatile manner. Individuals prone to developing diabetes or with overt type 2 diabetes are characterized by irregular oscillations of plasma insulin. Many factors have impact on insulin pulsatility such as age, insulin resistance and glycemic level. In addition, tiny glucose oscillations are capable of entraining insulin oscillations in healthy people in contrast to type 2 diabetic individuals emphasizing a profound disruption of the beta-cells in type 2 diabetes to sense or respond to physiological glucose excursions. A crucial question is how ∼1,000,000 islets, each containing from a few to several thousand beta-cells, can be coordinated to secrete insulin in a pulsatile manner. This is blatantly a very complex operation to control involving an intra-pancreatic neural network, an intra-islet communication and metabolic oscillations in the beta-cell itself. Overnight beta-cell rest, e.g. during somatostatin administration, improves the disordered pulsatile insulin secretion in type 2 diabetes. Acute as well as long-term administration of sulphonylureas (SU) leads to substantial amplification (∼50%) of the pulsatile insulin secretion in type 2 diabetes. This is probably cardinal in terms of governing the hepatic glucose release in type 2 diabetes. Whether sulfonylureas also improve the ability of the beta-cells to sense glucose fluctuations remains to be explored. Thiazolidinediones reduce the pulsatile insulin secretion without affecting regularity, but appear to improve the ability of the beta-cell to be entrained by small glucose excursions. Finally, similar to SUs, the incretin hormone GLP-1 also results in an augmented pulsatile burst mass in both healthy and diabetic individuals, in the latter group, however, without influencing the disorderliness of pulses. This review will briefly describe the high-frequency insulin pulsatility during physiologic and pathophysiologic conditions as well as the influence of some hypoglycemic compounds on the insulin oscillations.     

肾上腺髓质素加强高糖对自发性高血压大鼠胰岛β细胞的毒性作用

探讨高糖是否对自发性高血压大鼠 (SHR)和 Wistar- Kyoto(WKY)鼠胰岛 β细胞分泌功能具有抑制作用 ,肾上腺髓质素 (adrenomedullin,AM)能否加强此抑制作用。选取 6周龄 SHR鼠及 10周龄 WKY鼠各 10只 ,分离胰岛放入 12孔培养板内 (90个胰岛 /孔 )培养。先以含 5 .6 m mol/ L(m M)葡萄糖的 RPMI16 4 0培养基培养 1h,取出培养液。然后用含 2 0 m M葡萄糖及不同浓度 AM(分别是 0 ,10 - 8,10 - 7,10 - 6 M)的 RPMI 16 4 0培养基培养 1小时 ,取出培养液 ,放射免疫分析 (RIA)方法测定两次培养液的胰岛素含量。 SHR鼠的胰岛细胞经用不加 AM含 2 0m M葡萄糖的 16 4 0培养基培养 1h后 ,与用含 5 .6 m M葡萄糖的 16 4 0培养基培养 1h相比 ,其培养液中胰岛素含量明显降低 (分别是 19.9± 6 .6 vs6 0 .9± 33.6 m U/ L,P<0 .0 5 )。当用含 2 0 m M葡萄糖及不同浓度 AM的 16 4 0培养基培养时 ,随着 AM浓度的增加 ,培养液中的胰岛素含量进一步减少 (19.9± 6 .6 vs2 2 .2± 8.0 vs2 1.5± 5 .6 vs17.9± 3.6 m U/ L)。对照组 WKY鼠的胰岛细胞经上述相同方法处理后得出相似的结果。但 WKY鼠与 SHR鼠相比 ,其胰岛细胞经用含 5 .6 m M及 2 0 m M葡萄糖培养基培养后培养液中的胰岛素含量较高 (P<0 .0 1)。用高糖培养基培养     

Potentiation of glucose-induced insulin secretion in the perfused rat pancreas by porcine GIP (gastric inhibitory polypeptide), bovine GIP,and bovine GIP(139)

Porcine GIP (gastric inhibitory polypeptide) potentiates glucose-induced insulin secretion under a variety of experimental conditions. Recently GIP was isolated also from bovine intestine, and found to differ from porcine GIP by having isoleucine instead of lysine in position 37. We have compared the effects of porcine GIP to that of bovine GIP and bovine GIP_(]_₃₉₎ on glucose-induced insulin secretion from the perfused rat pancreas. We found that porcine GIP, bovine GIP, and bovine GIP_(l_₃₉₎ all strongly potentiated both first and second phases of glucose-induced insulin secretion (glucose concentration 6.7 mM; polypeptide concentration 1 nM). There was no significant difference between the polypeptides with regard to the potency to potentiate glucose-induced insulin secretion. We conclude that bovine GIP, as porcine GIP, potentiates glucose-induced insulin secretion, and that the insulinotropic activity of GIP is not confined to the last three amino acids at the C-terminal end.,     

Insulin suppresses intake without inducing illness in sham feeding rats

Insulin's effects on consumption were investigated in rats feeding with open gastric cannulas. Insulin produced small but statistically reliable decreases in sham intake. Intake was reduced during the one-hour sham feeding interval by 11 to 18%, however, the second, third and fourth 15-min intervals were reduced by 20 to 33%. An initial increase (first 15 min of sham feeding) following insulin injection offset somewhat insulin's suppressive effects on sham intake. All reductions were obtained by comparing sham intake following 0.1 to 0.75 U insulin per rat to intake following saline. When insulin or saline injections were paired with alternatively flavored sweetened condensed milk during sham feeding, subjects preferred the insulin-paired flavor in a subsequent two-bottle test. After just 6 complete pairings, insulin-paired, flavored milk was preferred at a ratio of almost six to one. The results indicate the effectiveness of insulin in inhibiting intake in a situation in which the actions of other potential satiety mechanisms are minimized. Additionally, insulin accomplishes this without inducing a flavor aversion for the milk sham consumed.     

Insulin sensitivity, insulin secretion, and metabolic and hormonal parameters in healthy women and women with polycystic ovarian syndrome

To study the contributions of body mass, body fat distribution and family history of type 2 diabetes mellitus to hyperinsulinaemia, insulin secretion and resistance in polycystic ovarian syndrome (PCOS), 17 lean (LC) and 17 obese (OC) healthy control subjects, and 15 lean (LPCOS) and 28 obese (OPCOS) women with PCOS were investigated. Waist:hip ratio (WHR), serum concentrations of sex steroids, glucose and insulin during a 75 g oral glucose tolerance test (OGTT), and insulin and C-peptide early phase secretion, and insulin sensitivity index using a euglycaemic hyperinsulinaemic clamp were assessed. The PCOS subjects had a higher mean WHR than the controls. A trend towards hyperinsulinaemia and impairment of insulin sensitivity (including the rates of both glucose oxidation and non-oxidation) was observed in LPCOS subjects, but only in OPCOS subjects were these changes significant. Early phase insulin secretion but not the early phase C-peptide secretion was increased in PCOS subjects compared to controls, suggesting that peripheral hyperinsulinaemia in PCOS women was mainly due to the observed lowered hepatic insulin extraction and insulin resistance in skeletal muscle. Moreover, the presence of a family history of type 2 diabetes did not affect early phase insulin or C-peptide secretion in the PCOS group. These results confirm and strengthen earlier contentions, that insulin resistance is a characteristic defect in PCOS and is worsened particularly by abdominal obesity.     

Insulin secretion induced by glucose and by stimulation of β2-adrenoceptors in the rat. Different sensitivity to somatostatin

The effects of somatostatin on insulin secretion stimulated by glucose or by the selective β₂-adrenoceptor agonist terbutaline were studied in vivo in the anaesthetized rat. Infusion of low doses of glucose (5mg/min) or terbutaline (2 μg/min) caused slight stimulation of insulin secretion, whereas infusion of higher doses of glucose (12.5mg/min) or terbutaline (200 μg/min) yielded higher rates of insulin release. In both instances plasma insulin concentrations were of comparable magnitudes immediately prior to somatostatin infusion. Somatostatin (0.1 μg/min) inhibited the insulin response to glucose and terbutaline, both at the low and high secretory rates. However, the inhibitory effect of somatostatin was much more pronounced on insulin release during glucose infusion than during infusion of terbutaline. Thus, at the high rate of insulin secretion somatostatin depressed plasma insulin by 46% during glucose and by 22% during terbutaline infusion. The results at the low rate of insulin secretion were 66% and 48%, respectively. Both at high and low secretory rates somatostatin depressed plasma insulin levels more potently during glucose infusion than during terbutaline infusion (P < 0.001 and P < 0.05, respectively). Furthermore, the plasma insulin levels during inhibition by somatostatin following terbutaline stimulation stabilized after approximately 10min of somatostatin infusion, whereas following glucose stimulation the insulin levels continued to decline. The results suggest that somatostatin inhibits insulin secretion via mechanisms that are more closely related to the insulin secretory pathway induced by glucose than to that induced by β-adrenoceptor agonists.     

Bromocriptine treatment over 12 years in acromegaly: effect on glucose tolerance and insulin secretion

Summary It is not known whether the beneficial effect of bromocriptine on glucose homeostasis in acromegaly is limited by a certain duration of therapy. To elucidate this problem, oral glucose tolerance tests were performed in 12 acromegaly patients before bromocriptine medication, under therapy (15.0 ± 6.8 mg/day for 12 ± 3 years), and during a 2-week drug withdrawal after long-term treatment. Initially altered glucose tolerance was normalized in 4 of 5 patients under bromocriptine therapy. During drug withdrawal the mean fasting glucose level and the mean glucose concentration at 120 min after oral glucose load increased from 5.05 ± 0.61 to 5.77 ± 0.78 mmol/1 and from 5.61 ±2.05 to 7.55 ± 3.05 mmol/1, respectively. A deterioration in glucose homeostasis was observed in 9 patients, and impaired glucose tolerance was ameliorated (but not to normal range) in 2 when bromocriptine was withdrawn. The proportion of alterations in glucose tolerance during drug withdrawal corresponded to that before the beginning of long-term bromocriptine treatment. Impaired glucose tolerance, observed in 2 patients under bromocriptine treatment, seemed to be compensated because a distinct elevation of glycosylated hemoglobin A_1c was not observed. Bromocriptine led to a significant decrease in basal as well as glucose-stimulated insulin levels, and growth hormone secretion during oral glucose load was reduced in all 12 patients. Similarly to the increased growth hormone secretion after drug withdrawal in 11 patients, a rise in glucose-stimulated insulin secretion was found in all patients; hereby, the mean insulin levels at 0 and 120 min during oral glucose load rose significantly from 7.5 ± 2.6 to 12.1 ± 5.1 mU/1 (P<0.01) and from 71.3±52.1 to 101.4±50.7 mU/1 (P<0.02), respectively. A direct relationship between disturbance in glucose homeostasis and degree of hypersomatotropism was not observed. Our data confirm that the beneficial effect of bromocriptine therapy on glucose homeostasis in selected patients with acromegaly is still present after dopaminergic treatment over a mean period of 12 years. Compared with the published rates on improved glucose homeostasis under octreotide, the effect of bromocriptine seems to be more favorable.Abbreviations AUC area under the curve - GH growth hormone - PRL prolactin Dedicated to Prof. Dr. N. Zöllner on the occasion of his 70th birthday     

Ontogeny of cephalic insulin release by the rat

Developmental aspects of cephalic insulin release in rats were evaluated by examining insulin secretion in response to the sweet taste of saccharin at different ages. A cephalic insulin response was present at the time of normal weaning (21–22 days) and by 34 days of age its magnitude was indistinguishable from that of adults. The early appearance of cephalic insulin release prompted a second study examining whether this response is present at birth; i.e., prior to any suckling experience. In newborn rat pups, no increase in plasma insulin was seen as a result of introduction of saccharin into the oral cavity. It was concluded that maturational and/or learning changes responsible for cephalic insulin release occur during the suckling period. The discussion concerned whether these changes involve maturation of the afferent loop, the efferent loop and/or learning as a consequence of the suckling experience.     

Plasma levels of somatostatin following a test meal in dogs Initial atropine resistant vagally mediated decrease of somatostain levels and increase of gastrin and insulin levels

Plasma levels of somatostatin like immunoreactivity (SLI), below referred to as somatostatin levels, were measured in peripheral plasma of conscious dogs. Basal somatostatin levels averaged 49±10 pM. Somatostatin as well as gastrin and insulin plasma levels were measured before and after feeding with and without prior atropinization. During the first 10 min after feeding somatostatin levels fell from 49±10 to 23±9 pM, whereas gastrin and insulin levels rose from 9±2 and 140±14 pM to 48±11 and 370±91 pM respectively. Atropine 0.01 or 0.1 mg/kg did not inhibit these responses. After the initial decrease, somatostatin levels rose again and peaked at around 60 min after feeding (110±24 pM). This secondary rise was completely abolished by atropine in both doses tried. Gastrin and insulin levels remained elevated throughout the experiments with and without atropine. It is suggested that gastrin release and HCI secretion are inhibited by a tonic outflow of gastric somatostatin during basal conditions. The process of feeding induces an atropine resistant, vagally mediated decrease in somatostatin release from the gastrointestinal tract and this decreased output of somatostatin facilitates initiation of meal-related endocrine and exocrine gastric secretions.