Insulin secretory response to different secretagogues in hyper- and hypothyroid mice

1981 ◽  
Vol 97 (4) ◽  
pp. 508-513 ◽  
Author(s):  
Bo Ahrén ◽  
Ingmar Lundquist
Keyword(s):  
Glucose Level ◽  
Plasma Glucose ◽  
Muscle Glycogen ◽  
Insulin Response ◽  
Liver Glycogen ◽  
Secretory Response ◽  
Thyroid State ◽  
Lower Glucose ◽  
Insulin Secretory Response

Abstract. The influence of long-term changes in thyroid state on insulin secretion was investigated in vivo in mice. Hyperthyroidism was induced by daily injections of i.-triiodothyronine and hypothyroidism by a single injection of 131I. Four different insulin secretagogues were used to characterize the insulin secretory response, i.e. glucose, the β2-adrenoceptor agonist terbutaline, the cholinergic agonist carbachol and the synthetic C-terminal octapeptide of cholecystokinin, CCK-8. In the hyperthyroid mice the plasma glucose level was moderately decreased. Despite this lower glucose level the insulin response to terbutaline and glucose were potentiated by about 200%. Insulin response to CCK-8 and carbachol was less enhanced, by about 100 and 50%, respectively. Liver and muscle glycogen levels were markedly reduced. The hypothyroid animals showed reduced insulin responses to all secretagogues; after terbutaline by 100%, after carbachol by 70%, after glucose and CCK-8 by 50%. Plasma glucose and muscle glycogen levels were normal, whereas liver glycogen levels were moderately enchanced. Insulin release induced by β-adrenoceptor stimulation was most markedly affected by the thyroid state, which thus may be of importance for the balance between the β- and α-adrenoceptors of the insulin cell. Since thyroid activity influenced the insulin response to all secretagogues it cannot be excluded that the thyroid state also exerts effects not related to the adrenoceptors.

Islet glucan-1,4-α-glucosidase: differential influence on insulin secretion induced by glucose and isobutylmethylxanthine in mice

1993 ◽  
Vol 138 (3) ◽  
pp. 391-400 ◽  
Author(s):  
A. Salehi ◽  
I. Lundquist
Keyword(s):  
Insulin Secretion ◽  
Insulin Release ◽  
Marked Reduction ◽  
Insulin Response ◽  
Indirect Evidence ◽  
Secretory Response ◽  
Isolated Pancreatic Islets ◽  
Enzyme Replacement ◽  
Insulin Secretory Response

ABSTRACT In previous in-vivo studies we have presented indirect evidence for the involvement of islet acid glucan-1,4-α-glucosidase (acid amyloglucosidase), a lysosomal glycogen-hydrolysing enzyme, in certain insulin secretory processes. In the present combined in-vitro and in-vivo investigation, we studied whether differential changes in islet acid amyloglucosidase activity were related to the insulin secretory response induced by two mechanistically different secretagogues, glucose and isobutylmethylxanthine (IBMX). It was observed that addition of the selective α-glucosidehydrolase inhibitor emiglitate (1 mmol/l) to isolated pancreatic islets resulted in a marked reduction of glucose-induced insulin release. This was accompanied by a pronounced suppression of islet activities of acid amyloglucosidase and acid α-glucosidase, whereas other lysosomal enzyme activities, such as acid phosphatase and N-acetyl-β-d-glucosaminidase, were unaffected. Furthermore, islets first incubated with emiglitate in the presence of high (16·7 mmol/l) glucose released less insulin than untreated controls in response to glucose in a second incubation period in the absence of emiglitate. In contrast, IBMX-induced insulin release was not influenced by emiglitate although accompanied by a marked reduction of islet activities of all three α-glucosidehydrolases. Basal insulin secretion (1 mmol glucose/1) was unaffected in the presence of emiglitate. In-vivo pretreatment of mice with highly purified fungal amyloglucosidase ('enzyme replacement'), a procedure known to increase islet amyloglucosidase activity, resulted in a greatly enhanced insulin secretory response to an i.v. glucose load. The increase in insulin release was accompanied by a markedly improved glucose tolerance curve in these animals. In contrast, enzyme pretreatment did not influence the insulin response or the blood glucose levels after an i.v. injection of IBMX. The data lend further support to our hypothesis that islet acid amyloglucosidase is involved in the multifactorial insulin secretory processes induced by glucose but not in those involving direct activation of the cyclic AMP system. The results also indicate separate, or at least partially separate, pathways for insulin release induced by glucose and IBMX. Journal of Endocrinology (1993) 138, 391–400

scholarly journals Gluconeogenesis from lactate in the developing rat. Studies in vivo

1972 ◽  
Vol 127 (3) ◽  
pp. 531-537 ◽  
Author(s):  
Richard G. Vernon ◽  
Deryck G. Walker
Keyword(s):  
Skeletal Muscle ◽  
Plasma Glucose ◽  
Muscle Glycogen ◽  
Half Life ◽  
Specific Radioactivity ◽  
Liver Glycogen ◽  
Plasma Lactate ◽  
Old Rats ◽  
Developing Rat

1. The specific radioactivity of plasma l-lactate and the incorporation of 14C into plasma d-glucose, liver glycogen and skeletal-muscle glycogen were measured as a function of time after the intraperitoneal injection of l-[U-14C]lactate into 2-, 10- and 30-day-old rats. 2. Between 15 and 60min after the injection of the l-[U-14C]lactate, the specific radioactivity of plasma lactate decreased with a half-life of 20–33min in animals at all three ages. 3. At all times after injection examined, the specific radioactivity of plasma glucose of the 2- and 10-day-old rats was at least fourfold greater than that of the 30-day-old rats. 4. Although 14C was incorporated into liver glycogen the amount incorporated was always less than 5% of that present in plasma glucose. 5. The results are discussed with reference to the factors that may influence the rate of incorporation of 14C into plasma glucose, and it is concluded that the rate of gluconeogenesis in the 2- and 10-day-old suckling rat is at least twice that of the weaned 30-day-old animal.

Metabolic and hormonal changes following endotoxin administration to diabetic rats

1982 ◽  
Vol 243 (1) ◽  
pp. R77-R81
Author(s):  
D. L. Kelleher ◽  
B. C. Fong ◽  
G. J. Bagby ◽  
J. J. Spitzer
Keyword(s):  
Plasma Glucose ◽  
Time Course ◽  
Glycogen Content ◽  
Metabolic Response ◽  
Insulin Response ◽  
Liver Glycogen ◽  
Diabetic Rats ◽  
Hormonal Changes ◽  
Glycogen Depletion ◽  
Endotoxin Administration

The aim of these investigations was to study the time course and cause of the altered metabolic response of diabetic rats to endotoxin administration. Escherichia coli endotoxin was administered to streptozotocin-diabetic and control normoglycemic rats. At 1, 2, 5, 8, and 24 h following endotoxin, animals were decapitated. Plasma samples were analyzed for glucose, lactate, insulin, glucagon, and corticosteroids. In addition, tissue glycogen content of liver and skeletal muscle was determined. Endotoxin caused an elevation of plasma glucose in both diabetic and normoglycemic rats by 1 h postinjection. The elevation was prolonged in diabetic rats for 8 h but lasted only 2 h in nondiabetic rats. Both endotoxin-treated groups demonstrated hyperlactacidemia following endotoxin. Endotoxin led to liver glycogen depletion in both diabetic and normoglycemic rats, whereas muscle glycogen content was only slightly affected. Plasma glucagon and corticosteroids rose immediately and remained elevated in both endotoxin-treated groups. A significant insulin response to rising plasma glucose was observed in nondiabetic but not in diabetic rats following endotoxin. These results suggest that the exaggerated and prolonged hyperglycemia observed in diabetic endotoxin-treated rats is due to hypersecretion of glucose-mobilizing hormones and elevated gluconeogenesis, unmatched by an adequate secretion of insulin to promote glucose uptake and utilization.

Ca2+ deficiency, selective alpha-glucosidehydrolase inhibition, and insulin secretion

1993 ◽  
Vol 265 (1) ◽  
pp. E1-E9 ◽  
Author(s):  
A. Salehi ◽  
I. Lundquist
Keyword(s):  
Insulin Secretion ◽  
Acid Phosphatase ◽  
Insulin Release ◽  
Insulin Response ◽  
Selective Inhibition ◽  
Half Maximal Effective Concentration ◽  
Insulin Secretory Response ◽  
Dose Dependent ◽  
Alpha Glucosidase

We investigated the relation between activities of islet glycogenolytic alpha-glucosidehydrolases and insulin secretion induced by glucose and 3-isobutyl-1-methylxanthine (IBMX) by means of suppressing 1) insulin release (Ca2+ deficiency) and 2) islet alpha-glucosidehydrolase activity (selective inhibition by the deoxynojirimycin derivative miglitol). Additionally, the in vivo insulin response to both secretagogues was examined. We observed that, similar to glucose-induced insulin release, islet glycogenolytic hydrolases (acid amyloglucosidase, acid alpha-glucosidase) were highly Ca2+ dependent. Acid phosphatase, N-acetyl-beta-D-glucosaminidase, or neutral alpha-glucosidase (endoplasmic reticulum) was not influenced by Ca2+ deficiency. In Ca2+ deficiency IBMX-induced insulin release was unaffected and was accompanied by reduced activities of islet alpha-glucosidehydrolases. Miglitol strongly inhibited glucose-induced insulin release concomitant with a marked suppression of islet alpha-glucosidehydrolase activities. Direct addition of miglitol to islet homogenates suppressed acid amyloglucosidase [half-maximal effective concentration (EC50) approximately 10(-6) M] and acid alpha-glucosidase. Acid phosphatase and N-acetyl-beta-D-glucosaminidase were unaffected. The miglitol-induced inhibition of glucose-stimulated insulin release was dose dependent (EC50 approximately 10(-6) M) and displayed a remarkable parallelism with the inhibition curve for acid amyloglucosidase. The in vivo insulin secretory response to glucose was markedly reduced in dystrophic mice (low amyloglucosidase), whereas the response to IBMX was unaffected. In summary, islet glycogenolytic hydrolases are Ca2+ dependent, and acid amyloglucosidase is directly involved in the multifactorial process of glucose-induced insulin release. In contrast the mechanisms of IBMX-stimulated insulin secretion operate independently of these enzymes. The effects of miglitol, a drug currently used in diabetes therapy, deserves further investigation.

Insulin response after treatment depends on fasting plasma glucose level in NIDDM

1994 ◽  
Vol 26 (2) ◽  
pp. 129-135
Author(s):  
Kazunari Matsumoto ◽  
Shoichi Akazawa ◽  
Norio Abiru ◽  
Mayumi Yano ◽  
Miwa Ishibasi ◽  
...  
Keyword(s):  
Glucose Level ◽  
Plasma Glucose ◽  
Fasting Plasma Glucose ◽  
Plasma Glucose Level ◽  
Insulin Response ◽  
Fasting Plasma Glucose Level ◽  
Fasting Plasma

Glucose turnover in 48-hour-fasted running rats

1987 ◽  
Vol 252 (3) ◽  
pp. R587-R593 ◽  
Author(s):  
B. Sonne ◽  
K. J. Mikines ◽  
H. Galbo
Keyword(s):  
Plasma Glucose ◽  
Muscle Glycogen ◽  
Lactate Production ◽  
Glucose Production ◽  
Liver Glycogen ◽  
Glucose Turnover ◽  
Feedback Mechanisms ◽  
Glycogen Stores ◽  
Resting Muscle ◽  
Fasted Rats

In fed rats, hyperglycemia develops during exercise. This contrasts with the view based on studies of fasted human and dog that euglycemia is maintained in exercise and glucose production (Ra) controlled by feedback mechanisms. Forty-eight-hour-fasted rats (F) were compared to fed rats (C) and overnight food-restricted (FR) rats. [3-3H]- and [U-14C] glucose were infused and blood and tissue sampled. During running (21 m/min, 0% grade) Ra increased most in C and least in F and only in F did Ra not significantly exceed glucose disappearance. Plasma glucose increased more in C (3.3 mmol/l) than in FR (1.6 mmol/l) and only modestly (0.6 mmol/l) and transiently in F. Resting liver glycogen and exercise glycogenolysis were highest in C and similar in FR and F. Resting muscle glycogen and exercise glycogenolysis were highest in C and lowest in F. During running, lactate production and gluconeogenesis were higher in FR than in F. At least in rats, responses of production and plasma concentration of glucose to exercise depend on size of liver and muscle glycogen stores; glucose production matches increase in clearance better in fasted than in fed states. Probably glucose production is stimulated by “feedforward” mechanisms and “feedback” mechanisms are added if plasma glucose decreases.

Effects of Acute Exposure to Bleached Kraft Pulpmill Effluent on Carbohydrate Metabolism of Juvenile Coho Salmon (Oncorhynchus kisutch) During Rest and Exercise

1975 ◽  
Vol 32 (6) ◽  
pp. 753-760 ◽  
Author(s):  
D. J. McLeay ◽  
D. A. Brown
Keyword(s):  
Plasma Glucose ◽  
Muscle Glycogen ◽  
Coho Salmon ◽  
Liver Glycogen ◽  
Plasma Lactate ◽  
Mean Values ◽  
Glucose Levels ◽  
Lactate Levels ◽  
Sugar Levels ◽  
Glycogen Stores

In the static study (no exercise), liver glycogen stores were unchanged during 12-h exposure to 0.8 of the 96-h LC50; longer exposures caused a progressive decrease to levels one fifth those of controls at 72 h. Plasma glucose levels in fish held in 0.8 LC50 effluent for 3–96 h were elevated; at 96 h, glucose had increased threefold. Mean values for plasma lactate were elevated significantly at 3, 6, 24, 72, and 96 h.In the exercise (swimming one body length per second)–rest study, muscle glycogen levels decreased 53–78% during exercise in water or effluent (0.7 LC50) for 4–12 h, and did not recover during 12-h rest in water. Muscle glycogen for fish exercised for 12 h in effluent and then rested for 4 or 12 h in effluent was lower compared to values for fish exercised in effluent and then rested in water. There was no difference in liver glycogen levels offish exercised in effluent or water for 4–12 h. Values of liver glycogen for fish exercised in effluent for 12 h and then rested for 4, 8, or 12 h in effluent decreased 60–70% compared to fish exercised in water for 12 h and then rested in water and by 55–65% from fish exercised in effluent for 12 h and rested in water for 4–12 h. Plasma glucose levels were elevated one- to fourfold during exercise in water or effluent. Fish resting in water for 4, 8, or 12 h following exercise in water had relatively stable glucose levels; whereas for fish exercised and then rested in effluent the glucose levels increased twofold during resting. Plasma lactate levels were elevated five- to sixfold during exercise in water or effluent for 4–12 h, declining to values 1–2 times those of stock fish within 4-h rest. Plasma lactate levels for fish exercised in effluent and then rested in effluent or water were continually higher than those for fish exercised and rested in water.It was concluded that measurement of carbohydrate metabolites, particularly blood sugar levels, in unexercised fish could prove useful as a rapid method for measuring toxicity of pulpmill effluents and other pollutants.

Involvement of capsaicin-sensitive nerves in regulation of insulin secretion and glucose tolerance in conscious mice

1994 ◽  
Vol 267 (4) ◽  
pp. R1071-R1077 ◽  
Author(s):  
S. Karlsson ◽  
A. J. Scheurink ◽  
A. B. Steffens ◽  
B. Ahren
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Insulin Response ◽  
Secretory Response ◽  
Sensory Nerves ◽  
Plasma Norepinephrine ◽  
Plasma Catecholamine ◽  
Intravenous Glucose ◽  
The Impact ◽  
Insulin Secretory Response

The impact of sensory nerves in glucose-stimulated insulin secretion and glucose tolerance was investigated in conscious mice treated neonatally with either capsaicin (Cap) or vehicle (Veh). At 10-12 wk after Cap, both the early (1 min) insulin secretory response to intravenous glucose (2.8 mmol/kg) (by 67%) and glucose elimination were potentiated (P < 0.05). In contrast, basal insulin, glucagon, and glucose were not affected by Cap. Plasma norepinephrine and epinephrine levels did not differ between Cap- and Veh-treated animals, whereas the increase in plasma insulin levels normally induced by alpha-adrenoceptor blockade by phentolamine was absent after Cap treatment. In isolated islets, the insulin secretory response to glucose (20 mmol/l), carbachol (0.1 mmol/l), or phentolamine (0.5 mmol/l) was not affected after Cap. It is concluded that sensory denervation by Cap results in increased glucose tolerance, which is in part because of a potentiated early insulin response to glucose. This potentiation does not seem secondary to altered plasma catecholamine levels or to altered islet secretory capacity. The results suggest rather that Cap-sensitive nerves, by a local effector function and/or as the afferent loop of a neural reflex, exert inhibitory influences on insulin secretion.

An effect of hyposmolarity on insulin release in vitro

1975 ◽  
Vol 228 (3) ◽  
pp. 706-713 ◽  
Author(s):  
WG Blackard ◽  
M Kikuchi ◽  
A Rabinovitch ◽  
AE Renold
Keyword(s):  
Insulin Secretion ◽  
Calcium Concentration ◽  
Insulin Response ◽  
Secretory Response ◽  
Calcium Gradient ◽  
Blocking Agents ◽  
Medium Osmolarity ◽  
Pump Activity ◽  
Insulin Secretory Response

An abrupt reduction of medium osmolarity by as little as 20 mosM evoked a discrete short-lived insulin secretory response from perifused chopped pancreas or isolated islets. The insulin response occurred earlier than that induced by either glucose or tolbutamide. None of the usual modifiers of insulin secretion significantly altered this secretory response. Glycolytic inhibitors, adrenergic agonists and blocking agents, cholinergic blocking agents, mitotic spindle inhibitors, and agents influencing sodium pump activity failed to alter hyposmolar-induced insulin secretion. Manipulation of the perifusion medium calcium concentration was the only procedure tested that influenced the secretory response. Perturbations of medium calcium concentration that increased the tissue-to-medium calcium gradient augmented the hyposmolar-induced insulin response and those that decreased tissue-to-medium calcium gradient greatly inhibited the response. The precise cause of the insulin response to a decrease in bathing fluid osmolarity remains undefined; however, the stimulus is not specific for insulin because increases in glucagon and amylase were also elicited by the hyposmolar stimulus.

A NEW PRINCIPLE FOR THE COMPARISON OF INSULIN SECRETORY RESPONSES

1973 ◽  
Vol 74 (3) ◽  
pp. 524-541 ◽  
Author(s):  
Klaus Johansen
Keyword(s):  
Blood Glucose ◽  
Glucose Tolerance ◽  
Beta Cells ◽  
Plasma Insulin ◽  
Insulin Response ◽  
Secretory Response ◽  
Obese People ◽  
Intravenous Glucose ◽  
Large Groups ◽  
Insulin Secretory Response

ABSTRACT In an attempt to circumvent the difficulties inherent in the use of insulin/glucose ratios a new principle for the comparison of insulin secretory resonses has been developed. From large groups of obese and non-obese people subjects are selected so that the subgroups ultimately formed are comparable with regard to age and to their degree of glucose tolerance. This means that the blood glucose curves of the two groups are merging and that the beta cells are subjected to identical glycaemic stimuli. The study shows that obese young non-diabetics and obese young and old diabetics exhibit an augmented insulin response to stimulation with oral and intravenous glucose and to intravenous tolbutamide. No increase in plasma insulin secretory response is, however, demonstrable in obese, old non-diabetics.

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