Administration Of Regular Insulin Research Articles

Dietary Factors Associated with Glycemic Control in Children and Adolescents with Type 1 Diabetes.

Type 1 diabetes mellitus (T1DM) is a chronic metabolic disease that results from the autoimmune destruction of pancreatic β-cells, leading to insulin deficiency and hyperglycemia. It is a common chronic disease in childhood, with a prevalence of 1 in 300 children in the United States and an increasing incidence of 2-5% annually, worldwide. Managing T1DM requires regular insulin administration, adjustment of food intake and exercise, and a comprehensive understanding of nutrition. This review aims to explore the relationship between dietary factors, physical activity, obesity, genetics, and glycemic control in children and adolescents with T1DM. To conduct this review, we conducted a thorough search of publications from December 2004 through April 2022 using PubMed, ScienceDirect, and Embase databases. Key topics included obesity, children, adolescents, nutrients, carbohydrates, proteins, fat, water-soluble vitamins, fat-soluble vitamins, dietary patterns, fruits and vegetables, physical activity, genetics, food habits, carbohydrate count and environmental factors.

Clinicodemographic profile of diabetic ketoacidosis and its management in hospitalized children – A prospective study

Background: Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in children with Type 1 diabetes (T1DM). In developing countries, mortality is between 6 and 24%. Recent studies have documented that DKA in association with cerebral edema (CE) accounted for a mortality of 1–24% with a high rate of permanent neurologic morbidity. Objective: The objective of the study was to study the demographic profile, clinical presentation at the time of admission, management, and complications of patients diagnosed as T1DM with DKA. Materials and Methods: A prospective observational study was conducted among children admitted in PICU MGM hospital, Warangal, Telangana between December 2016 and November 2018. Children up to the age of 18 years diagnosed as T1DM who presented with DKA were included in the study. Sociodemographic profile, dietary intake, and treatment history of children were collected using a pre-designed pro forma. Clinical features and management were noted. Results: A total of 51 children were included in the study. Among them, 32 (62.74%) cases were newly diagnosed and 19 (37.2%) were previously diagnosed. A majority of the children belonged to lower socioeconomic status with 40% of the children suffering from severe grade of malnutrition. Classical symptoms of polyuria, polydipsia, and polyphagia were observed in 32 patients (62.74%). Vomiting was observed in 59% of cases, tachypnea in 82.35%, and abdominal pain in 29.41% of cases. About 54.90% of cases presented with severe and 33.3% with moderate DKA. Administration of regular insulin was the main modality of management in all cases. The major complication observed was hypoglycemia followed by cerebral edema. Conclusion: Cerebral edema with septic shock is a life-threatening complication of patients suffering with DKA. Active management with regular insulin can avert major complications and can lead to better outcomes.

Kebutuhan perawatan berpusat keluarga dalam manajemen diabetes pada anak dengan diabetes melitus

Diabetes mellitus (DM) is a serious disease that has the potential to cause complications and affect all ages, including children. Diabetes care management is needed to maintain blood glucose levels at an adequate level. Children, especially at an early age, have an inability to carry out various tasks related to proper diabetes care management. Family centered care is one strategy to empower families in diabetes care management to prevent complications. The purpose of this study was to identify the needs of parents in the management of diabetes care in children with DM type 1. This study was conducted in one hospital in Bandung. The type of research used is descriptive quantitative. This study used a total sampling technique to obtain 25 parents with children with DM. Data was collected using a Diabetic Care Needs Assessment Tool with 23 questions that were seen through the difficulty level of parents in meeting those needs. Data were analyzed using frequency distribution and percentage. The results obtained data on family centered care needs in the management of diabetes in children ranging from the most difficult to be fulfilled to those that were not difficult to fulfill in terms of the proportion of parents who stated it was information and education needs (32%), emotional needs (24%), collaboration and collaboration needs (20%), and psychosocial needs (8%). The most difficult thing for more than half the parents of children with diabetes mellitus is the information and education needs. Nurses can help parents to meet the management needs of diabetes care in children, especially information and education that parents need. Education that can be provided by nurses, including regular insulin administration, regular blood glucose control, physical exercise activities, appropriate menus, and self-management or self-care in children to improve the quality of life in children with diabetes.

Effect of a Standardized Treatment Panel on Hypoglycemic Events in Hospitalized Acute Hyperkalemic Patients Treated With Intravenous Regular Insulin.

Purpose: Regular insulin is a commonly utilized treatment option for acute hyperkalemia. Despite its benefit, hypoglycemia and associated morbidity/mortality remain important concerns. This institution recently created a treatment panel to standardize regular insulin dosing (0.1 unit/kg) and blood glucose (BG) monitoring in patients with acute hyperkalemia. The purpose of this study is to investigate whether the order panel reduces hypoglycemic events in adults treated with intravenous (IV) regular insulin for hyperkalemia and to determine the effect the treatment panel has on regular insulin dosing, serum potassium, BG monitoring, and dextrose supplementation. Methods: This retrospective study was performed at a single academic medical center. Adults receiving IV regular insulin for acute hyperkalemia were included if BG was assessed prior to and following regular insulin administration. Primary outcome was hypoglycemia within 4 hours of regular insulin administration. Secondary outcomes were the change from baseline serum potassium, frequency of severe hypoglycemia, BG checks within 30 minutes prior to and within 4 hours following insulin administration, regular insulin dosing, and administration of dextrose 50% in water (D50W) following regular insulin administration. Hypoglycemia and severe hypoglycemia were defined as a BG concentration of <70 mg/dL and <50 mg/dL, respectively. Results: One hundred sixty-five patients were included; 75 using the treatment panel and 90 not. Patients using the treatment panel received a lower median (interquartile range [IQR]) regular insulin dose (.10 [0.09-0.10 unit/kg] vs 0.11 [0.09-0.14 unit/kg], P = .004) and had more frequent BG checks during the 4 hours following regular insulin administration (median [IQR]: 4 [3-5] vs 2 [1-3], P < .001). Hypoglycemia (13.3% vs 27.8%, P = .024) and severe hypoglycemia (2.7% vs 11.1%, P = .038) occurred less frequently with the treatment panel. Similar decreases in serum potassium were noted following IV regular insulin administration. Conclusions: Acute hyperkalemic patients utilizing a standardized treatment panel for the dosing and monitoring of IV regular insulin experienced fewer hypoglycemic and severe hypoglycemic episodes and had similar potassium lower effects. The treatment panel decreased regular insulin dosing and increased BG monitoring prior to and following regular insulin administration.

Subcutaneous regular insulin for the treatment of diabetic ketoacidosis in children.

Diabetic ketoacidosis (DKA) treatment protocols vary, however low-dose intravenous administration of regular insulin is the standard care for replacing insulin in most centers. Few studies, the majority in adults, demonstrated subcutaneous injection of rapid-acting insulin every 1-2 hours to be a valid alternative. To evaluate the efficacy and safety of subcutaneous regular insulin administered every 4 hours in pediatric DKA in a clinical setting. A retrospective chart review was conducted. Charts of all children treated with subcutaneous regular insulin for DKA and pH ≥ 7.0, between 2007 and 2010, were reviewed. Seventy-six DKA episodes in 52 patients were included. Data regarding clinical characteristics, response to treatment, and the occurrence of complications were analyzed. DKA episodes in patients with new-onset diabetes and in those with established diabetes were compared. Mean age was 11.6 ± 4.0 yr. Eighteen episodes occurred in children with new-onset diabetes. In all episodes, our protocol resulted in recovery from DKA. Median time to DKA resolution (pH > 7.30, HCO3 > 15) was 10.3 (5.5, 14.2) h. The median total insulin dose was 0.05 (0.04, 0.06) (unit/kg/h). During DKA treatment, hypoglycemia occurred in one episode and hypokalemia, mostly mild, was documented in 14. No cardiac arrhythmias, incidents of cerebral edema, or mortality occurred. Subcutaneous regular insulin administered every 4 hours is an effective and safe alternative for the insulin treatment of DKA with pH > 7.0 in children. Such treatment has the potential to simplify insulin administration when compared to either intravenous regular insulin or q1-2 hour subcutaneous rapid insulin and reduce both patient inconvenience and admission costs.

Evaluation of glucose response to 3 types of insulin using a continuous glucose monitoring system in healthy alpacas.

BackgroundPersistent hyperglycemia is common in alpacas and typically requires insulin administration for resolution; however, little is known about alpacas’ response to different insulin formulations.ObjectivesTo evaluate the effects of 3 insulin formulations on blood glucose concentrations and the use of a continuous glucose monitoring (CGM) system in alpacas.AnimalsSix healthy alpacas.MethodsThe CGM was installed in the left paralumbar fossa at the start of this crossover study and recorded data every 5 minutes. Regular insulin, NPH insulin, insulin glargine, and dextrose were administered to each alpaca over a 2‐week period. Blood samples were collected for glucose testing at 0, 1, 2, 4, 6, 8, and 12 hours, and then every 6 hours after each administration of insulin or dextrose. Data were compared by using method comparison techniques, error grid plots, and ANOVA.ResultsBlood glucose concentrations decreased most rapidly after regular insulin administration when administered IV or SC as compared to the other formulations. The NPH insulin produced the longest suppression of blood glucose. The mean CGM interstitial compartment glucose concentrations were typically lower than the intravascular compartment glucose concentrations. The alpacas had no adverse reactions to the different insulin formulations.Conclusions and Clinical ImportanceThe NPH insulin might be more appropriate for long‐term use in hyperglycemic alpacas because of its extended duration of action. A CGM is useful in monitoring glucose trends and reducing blood collection events, but it should not be the sole method for determining treatment protocols.

Management of acute hyperglycemic emergencies: focus on diabetic ketoacidosis.

Management of acute hyperglycemic emergencies: focus on diabetic ketoacidosis.

Tacrolimus and sirolimus have distinct effects on insulin signaling in male and female rats

Although the contribution of the immunosuppressants tacrolimus (TAC) and sirolimus (SIR) to the development of posttransplant diabetes mellitus (PTDM) are being increasingly recognized, the mechanisms of immunosuppressant-induced hyperglycemia are unclear. SIR induces insulin resistance predominantly, but is associated with β-cell dysfunction in rodents. TAC affects islet function but is associated with worsening insulin sensitivity in a few, and improvement in some, clinical studies. We sought to clarify the contributions of TAC and SIR to insulin resistance and islet function. Four groups of male and female Sprague-Dawley rats received TAC, SIR, TACandSIR, or control for 2weeks. All rats were administered an oral glucose challenge at the end of treatment. Half the groups were sacrificed 10minutes after administration of regular insulin whereas the other half did not receive insulin before sacrifice. Liver, pancreas, fat, and muscle were harvested subsequently. Quantification of Western blots revealed that SIR and TACplus SIR suppressed the phospho-Akt (pAkt)-to-Akt ratios in liver, muscle, and fat compared with control, regardless of sex. TAC alone did not impair the pAkt-to-Akt ratios in any of the tissues in male and female rats. β-Cell mass was reduced significantly after TAC treatment in male rats. SIR did not affect β-cell mass, regardless of sex. Our study demonstrated very clearly that SIR impairs insulin signaling, without any effect on β-cell mass, and TAC does not impair insulin signaling but reduces β-cell mass. Our efforts are key to understanding the mechanisms of immunosuppressant-induced hyperglycemia and to tailoring treatments for PTDM.

Insulin-induced hypoglycemia and stress oxidative state in healthy people

The purpose of this study is to assess the immediate effects of insulin-induced hypoglycemia on the natural antioxidant superoxide dismutase activity, malondialdehyde concentration, total antioxidative capacity and total thiol group concentration in young healthy subjects. In this clinical trial, 16 healthy men with the mean age of 29.3 ± 5.3 years (range 21-39 years) became volunteers to participate the study. Hypoglycemia was induced by intravenous administration of regular insulin 0.1 U/kg. Before and after inducing hypoglycemia, SOD activity was determined in red blood cells, whereas the MDA concentration was determined by thiobarbituric acid reactive substance method, total thiol groups by high-performance liquid chromatography method and total antioxidant capacity by ferric reducing/antioxidant power. A significant increase was seen in the TBARS levels following insulin-induced hypoglycemia (0.19 ± 0.07 vs. 0.38 ± 0.16 nmol/g, P < 0.001), while a significant decrement occurred in the antioxidant power (FRAP value) (321.4 ± 63.4 vs. 231.4 ± 57.5, P < 0.001), total thiol concentration (2.3 ± 0.8 vs. 1.3 ± 0.5, P = 0.001) and SOD enzyme activity (29.4 ± 8.2 vs. 23.1 ± 6.1, P < 0.001) subsequent the hypoglycemia with insulin.

Use of a constant rate infusion of insulin for the treatment of hyperglycemic, hypernatremic, hyperosmolar syndrome in an alpaca cria

A 3-day-old 9.5-kg (21-lb) female alpaca cria was examined because of lethargy and anorexia. Physical examination revealed hyperthermia, muscle fasciculations, and tremors of the head. Seizures were also observed, which indicated CNS dysfunction. Hyperosmolar syndrome (HOS) was diagnosed on the basis of hyperglycemia, hypernatremia, azotemia, high plasma osmolarity, and metabolic acidosis. A constant rate infusion of regular insulin was administered with hypo-osmolar fluids to treat HOS, and blood glucose and sodium concentrations were successfully lowered. Neurologic deficits resolved with treatment, and the cria was discharged 11 days after admission. Administration of insulin as a bolus in addition to hypo-osmolar fluids has been advocated in the management of neonatal camelids with HOS. Administration of regular insulin via a constant rate IV infusion was used to successfully manage a neonatal camelid with HOS. This form of insulin administration may allow more control of glucose kinetics in these patients.

Biokinetics of buccal spray insulin in patients with type 1 diabetes

Objective To evaluate the metabolic effect of buccal spray insulin compared with subcutaneous regular insulin in patients with type 1 diabetes. Research Design and Methods This study compared plasma glucose, insulin, and C-peptide levels in 18 patients with type 1 diabetes treated with subcutaneous regular or buccal spray insulin on 2 consecutive mornings. On day 1, patients were treated with their usual subcutaneous regular insulin regimens. On day 2, patients received buccal spray insulin. In the morning of both days 1 and 2, patients received a standard meal of 630 kJ. No intermediate or long-acting insulin was administered to patients on the morning of the test. Blood samples were collected for up to 4 hours for biokinetic analysis. In a subset of 3 patients, premeal buccal spray insulin was administered for 2 entire consecutive days. In these patients, glucose levels were monitored using the glucose sensor monitoring system. Results Overall, there were no statistically significant differences in glucose, insulin, or C-peptide levels measured after administration of subcutaneous vs buccal spray insulin. However, at 90 and 120 minutes after subcutaneous regular insulin administration, significantly higher insulin levels and more prolonged hypoglycemic effect were detected compared with buccal spray insulin administration. In the 3 patients who received 1 day of regular and 2 entire days of buccal spray insulin, no significant differences were observed in glucose levels during the 3 days of glucose sensor monitoring. Conclusions Insulin administered via the buccal spray formulation is as effective as the subcutaneous route in lowering blood glucose levels.

Menor incidência de hipoglicemia noturna com o uso de insulina lispro comparada à insulina humana regular no tratamento de pacientes com diabetes do tipo 1

Insulina lispro é um análogo da insulina humana de ação e duração rápida, que mimeíiza o perfil fisiológico da insulina após uma refeição. Avaliamos a segurança e eficácia da insulina lispro em comparação com a insulina humana regular em um estudo multicêntrico, randomizado e cruzado em 27 diabéticos tipo 1 em uso de insulina humana NPH e regular (idade mediana = 16 anos). Após uso de insulina lispro ou regular por 2 meses, fez-se a transferência para a outra insulina por mais 2 meses mantendo-se a insulina NPH basal. Não houve diferença em relação à excursão prandial da glicemia da hemoglobina glicosilada A1C, comparando-se os 2 grupos (lispro e regular). O decréscimo percentual relativo da glicemia foi significantemente maior com insulina lispro no período do almoço, na primeira fase do estudo (p&lt;0,02). O número total de episódios hipoglicêmicos não foi diferente, comparando os 2 grupos. Houve, porém, uma redução significante na incidência de hipoglicemia noturna e na madrugada com o uso inicial de lispro (p&lt;0,05). Com o uso inicial de insulina regular, houve incremento na incidência de hipoglicemia noturna (p=0,038), com redução posterior na incidência da hipoglicemia com insulina lispro (p=0,04). Ao final do estudo, 68% dos pacientes referiram preferência e maior comodidade com insulina lispro em relação à insulina regular. A insulina lispro se mostrou uma opção segura e eficaz, com menor incidência de hipoglicemia noturna em diabéticos tipo 1. Uma otimização do regime de insulina basal é necessária para melhora do controle glicêmico, quando em uso de uma insulina de ação rápida.

Knowledge on diabetes and performance among health professionals in non-diabetological departments.

We tested the level of knowledge on diabetes and professional skills in a group of 60 non-diabetological health care professionals at the Policlinic of Pisa regarding the recognition and treatment of hypoglycaemia, the storage, mixing and administration of insulin, blood glucose stick monitoring, and the prevention and treatment of diabetic foot. The evaluation was carried out using a multiple-choice questionnaire and observation of the subjects, performance by means of pre-defined observation schedules, during the preparation and administration of a blend of rapid-intermediate insulin, the use of blood glucose sticks and the management of a simulated hypoglycaemic crisis. As regards hypoglycaemia, 90% of subjects did not give a correct definition, 88.3% were unaware of the existence of asymptomatic hypoglycaemia, and 96.6% did not give a complete answer as to the treatment of hypoglycaemia. For insulin, 51.7% did not know the standards for correct storage of insulin, 88.3% did not know the difference between "clear" and "opaque" insulins, and 91.7% ignored the required interval between administration of regular insulin and meals. For foot care, 45% admitted that the problems with diabetics' feet were frequently not controlled, and between 21.7% and 63.3% did not known the hygiene rules for feet. Assessment of the performance of the subjects using schedules revealed incorrect use of sticks and administration of insulin (80.2% mixed and 92.4% injected the insulin incorrectly). There is clearly a need for education of non-diabetological health professionals regarding the disease. This is supported by the health professionals themselves, 94.5% of whom wished to participate in a course on diabetes.

Absorption kinetics of regular insulin in dogs with alloxan-induced diabetes mellitus

SUMMARY The absorption kinetics of porcine regular insulin following iv, im, and sc administration were evaluated in 10 dogs with alloxan-induced diabetes mellitus. Plasma immunoreactive insulin (iri) concentrations were evaluated immediately prior to and at 10, 20, 30, 45, 60, 90, 120, 180, and 240 minutes following iv administration; and immediately prior to and every 30 minutes for 2 hours and then every hour for 6 hours following im and sc administration of 0.55 U of porcine regular insulin/kg of body weight. Model-independent pharmacokinetic analysis was performed on each data set. Plasma iri concentration declined rapidly after iv administration of regular insulin and then returned to baseline iri concentration by 3.2 ± 0.8 hours. The absorption kinetics following iv administration of regular insulin were similar to those found in earlier studies in healthy dogs and human beings. The im and sc routes of regular insulin administration resulted in a pharmacologic concentration of iri at 30 minutes. The peak mean (± SD) plasma iri concentration was significantly (P &lt; 0.05) greater following sc administratin than it was following im administration of regular insulin (263 ± 185 and 151 ± 71 IμU/ml, respectively). The time of the peak plasma iri concentration (68 ± 31 minutes and 60 ± 30 minutes) and the time to return to baseline plasma iri concentration (5.8 ± 1.2 hours and 5.8 ± 1.3 hours) were not significantly different following sc and im administration of regular insulin, respectively. The absorption kinetics following sc administration of regular insulin were similar to those found in earlier studies in healthy dogs and human beings. The absorption kinetics following im administration of regular insulin differed from those found in earlier studies and was similar to the absorption kinetics of regular insulin administered sc in this study. The reasons for this similarity were not readily apparent.

Brain 3-methoxytyramine varies inversely with blood glucose in decapitated rats

Concentrations of the dopamine metabolite, 3-methoxytyramine, were decreased significantly in the corpus striatum and nucleus accumbens of rats 30 min after the IP injection of D-glucose (2 g/kg). Conversely, 90 min after the administration of regular insulin (6 U/kg), significant increases in the concentrations of 3-methoxytyramine were observed in these two brain regions. Brain levels of the major metabolites of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid, did not correlate well with blood glucose concentration. The significant negative correlation of blood glucose with striatal and accumbens 3-methoxytyramine suggests an inverse relationship between dopamine metabolism and blood glucose concentration, that may be secondary to decapitation-induced anoxia.

Studies of the regulation of the hypothalamic-pituitary-adrenal axis in sheep with hypothalamic-pituitary disconnection. I. Effect of an audiovisual stimulus and insulin-induced hypoglycemia.

These studies were undertaken to characterize the secretion of adrenocorticotropin (ACTH), immunoreactive (ir) beta-endorphin (ir-beta-EP) and ir alpha-melanocyte-stimulating hormone (ir-alpha-MSH) from the surgically isolated ovine pituitary in response to an audiovisual stress (barking dog, 3 min) and insulin hypoglycemia. The studies were performed in 4 ovariectomized, hypothalamo-pituitary-disconnected (HPD) and 4 sham-HPD ewes bearing indwelling jugular venous catheters. Basal concentrations of the three pro-opiomelanocortin (POMC) peptides and plasma cortisol were significantly increased in the HPD animals. When the control ewes were exposed to the audiovisual stimulus, plasma ACTH, ir-beta-EP and ir-alpha-MSH levels were increased 2.5-, 10-, and 5-fold 1 min after the stress; plasma cortisol attained maximal values at 5 min. In contrast, plasma levels of the three POMC peptides were not significantly increased in the HPD animals, although a rise in plasma cortisol occurred. The administration of regular insulin (5 units/kg i.v.) to control ewes caused plasma ACTH, ir-beta-EP, and ir-alpha-MSH levels to increase 17-, 22-, and 67-fold at 50 min; plasma cortisol values were maximal at 60 min. In contrast, the elevated basal levels of POMC peptides in the HPD animals were not significantly increased by the hypoglycemia, but a significant elevation of plasma cortisol was seen. We conclude that: (1) the increase in ACTH in intact animals after an audiovisual emotional stress and hypoglycemia, and the abolition of this increase by HPD, indicates that both stimuli, each acting through distinct neuroanatomical pathways, increase the net corticotropin-releasing activity of the hypothalamus; (2) the rise in plasma cortisol in HPD animals after stress suggests that peripheral humoral factors may release additional small amounts of ACTH from the anterior pituitary, and (3) the finding of increased basal ACTH levels after HPD suggests that POMC peptide synthesis and secretion by the anterior pituitary is tonically regulated by an inhibitory factor of hypothalamic origin.

Reduced plasma high density lipoprotein-cholesterol concentrations need not increase when hyperglycemia is controlled with insulin in noninsulin-dependent diabetes mellitus.

The ability of intensive insulin treatment to increase plasma high density lipoprotein (HDL)-cholesterol levels was evaluated in 12 patients with noninsulin-dependent diabetes mellitus. Patients were treated for 6 weeks with one daily morning injection of ultralente insulin, in combination with administration of regular insulin before breakfast, lunch, and dinner. The mean (+/- SEM) fasting plasma glucose concentration fell from 289 +/- 21 to 122 +/- 9 mg/dl (P less than 0.001), and the mean hourly postprandial glucose concentration fell from 313 +/- 24 to 102 +/- 7 mg/dl (P less than 0.001). In addition, insulin treatment was associated with a reduction in both fasting plasma triglyceride (256 +/- 45 to 137 +/- 18 mg/dl; P less than 0.001) and cholesterol (224 +/- 25 to 199 +/- 19 mg/dl; P less than 0.05) concentrations. However, plasma HDL-cholesterol concentrations, which were low to begin with, did not rise in association with excellent glycemic control. These results demonstrate that hyperglycemia and hypertriglyceridemia can be effectively reduced by an aggressive program of insulin treatment in patients with noninsulin-dependent diabetes mellitus, but this intervention need not lead to an improvement in the abnormal HDL-cholesterol metabolism in these patients.

Dietary self-selection in insulin-injected hamsters

Adult male golden hamsters were given access to a variety of nutrient sources and were observed following the administration of regular insulin. It was hypothesized that if insulin produced hyperphagia in hamsters by the activation of a glucoprivic feeding mechanism, a selective increase in carbohydrate consumption would be observed. All animals received subcutaneous injections of 10, 30, 50 and 100 units/kg of insulin as well as a control injection of saline. Food consumption was recorded at +3, +6 and +24 hours after injections. In Experiment 1 hamsters having continuous access to Purina lab chow, fat (Crisco) and sucrose (sugar cubes) increased their total caloric consumption in response to insulin, but did not do so by selectively increasing their carbohydrate intake. In Experiment 2 hamsters maintained on Purina chow and sugar cubes consistently increased their carbohydrate intake as well as their total caloric consumption in response to insulin, but again the increase in carbohydrate intake was not selective; increased consumption of both sugar cubes and Purina chow occurred, and neither the proportion of total calories derived from carbohydrate nor the proportion of total calories derived from sugar cubes was affected by insulin administration. The results support the conclusion that insulin-induced hyperphagia in hamsters results from the activation of a non-glucoprivic feeding mechanism.

Characteristics of insulin-induced hyperphagia in the golden hamster

Two experiments were performed to investigate in some detail the behavioural and metabolic effects of the administration of regular insulin to golden hamsters. In Experiment 1 dose-response curves describing the effects of insulin upon both food intake and plasma glucose (PG) were generated. Dosages of less than 20 units/kg did not cause increases in food intake, while dosages of 10 units/kg or greater produced significant hypoglycemia at +6 hr post-injection. There was also a significant inverse linear relationship (r=−.528) between individual hamsters' food intakes and PG levels over the range of insulin dosages. It Experiment 2, insulin (30 units/kg) caused increases in meal frequency but not in meal size, and hyperphagia developed within +3 hr of insulin administration. When food was not available, insulin caused PG levels to fall below control levels at +1 hr and to remain depressed until at least +6 hr post-injection. However when hamsters were allowed to eat, PG did not fall significantly below control levels until +3 hr and began to recover at +5 hr post-injection. Results are discussed in relation to several apparent peculiarities in the hamster's behavioural response to regular insulin, specifically the small magnitude and the slow development of insulin-induced hyperphagia, and the hamster's relative insensitivity to the hyperphagic effect of insulin.

Dopaminergic stimulation and inhibition of growth hormone secretion in normal man: studies of the pharmacologic specificity.

We have previously reported that dopamine (DA) stimulates basal GH secretion, but blunts the response to hypoglycemia. Because the pharmacological specificity of these dual actions has never been determined, a four-part study was undertaken. Before the administration of regular insulin (0.1 U/kg), male subjects received saline, DA or the DA agonist bromocriptine either alone or during dopaminergic blockade with metoclopramide. DA and bromocriptine increased GH levels comparably, and pretreatment with metoclopramide abolished this response [control, 2.9 +/- 0.7 (+/- SE); DA, 12.8 +/- 3.2 (P less than 0.01); bromocriptine, 13.0 +/- 3.4 (P less than 0.05); bromocriptine plus metoclopramide, 4.8 +/- 1.4 ng/ml (NS compared to control; P less than 0.05 compared to bromocriptine)]. Both DA and bromocriptine significantly inhibited the GH response to hypoglycemia [peak increment: control, 35.2 +/- 4.8; DA, 7.5 +/- 1.8 (P less than 0.001); bromocriptine, 13.7 +/- 3.2 ng/ml (P less than 0.05)], while pretreatment with metoclopramide restored GH secretion to normal (24.5 +/- 6.8; NS compared to control). Similar results were obtained comparing the mean GH peaks and areas under the curve. While there was no correlation in the hypoglycemic GH responses between the control and dopaminergic studies, the blunting effects of dopamine and bromocriptine were highly correlated (r = 0.93; P less than 0.001). Consequently, under basal conditions, DA and bromocriptine stimulate GH to a similar degree and diminish the GH response to hypoglycemia comparably. Pretreatment with the DA antagonist metoclopramide returns GH secretion to normal by preventing the increase after bromocriptine and restoring the hypoglycemia-medicated rise. Therefore, the dual actions of DA on GH secretion are mediated by a dopaminergic mechanism, since they are mirrored by a specific DA agonist and prevented by a DA antagonist.