Alterations in pulsatile insulin secretion in the Zucker diabetic fatty rat

1994 ◽  
Vol 267 (2) ◽  
pp. E250-E259 ◽  
Author(s):  
J. Sturis ◽  
W. L. Pugh ◽  
J. Tang ◽  
D. M. Ostrega ◽  
J. S. Polonsky ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Spectral Power ◽  
Pulse Amplitude ◽  
Ringer Solution ◽  
Cellular Level ◽  
Diabetic Rats ◽  
Male Rats ◽  
Perfused Pancreas ◽  
Isolated Perfused Pancreas ◽  
Pulsatile Insulin Secretion

Insulin secretion from the isolated perfused pancreas is characterized by pulses occurring every 5-15 min. The present experiments were performed to explore the role of glucose in regulating these pulses. The pancreata from 12 Wistar (W), 12 Zucker diabetic fatty (ZDF), and 6 nondiabetic lean Zucker control (ZC) male rats were isolated and perfused at 37 degrees C with an oxygenated Krebs Ringer solution containing bovine serum albumin and glucose. In W and ZDF, insulin secretion was pulsatile during constant glucose, as assessed by pulse analysis (ULTRA). The pulse period in W was significantly shorter than in ZDF (7.1 +/- 0.6 vs. 14.7 +/- 1.0 min; P < 0.001), whereas the median relative pulse amplitude was not different. When glucose was administered as a series of 10-min sine waves, spectral analysis showed that the normalized spectral power at 10 min was greater in W and ZC compared with ZDF (34.2 +/- 5.9 and 32.9 +/- 2.9 vs. 3.2 +/- 0.9; P < 0.0001), demonstrating entrainment of the insulin pulses to the exogenous glucose oscillations in W and ZC but not in ZDF. Furthermore, in ZDF, the insulin secretory rates were not higher when 28 mM rather than 7 mM glucose were used. In additional studies, islets of Langerhans from one W, three ZDF, and three ZC rats were isolated and perifused using an oscillatory glucose concentration. Single and groups of islets were studied. Islets from diabetic rats demonstrated the same lack of entrainment by glucose seen in the perfused pancreas, suggesting that the defect is at the cellular level.(ABSTRACT TRUNCATED AT 250 WORDS)

INSULIN SECRETION OF THE ISOLATED PERFUSED PANCREAS OF THE CHINESE HAMSTER (CRICETULUS GRISEUS)

1974 ◽  
Vol 76 (2) ◽  
pp. 302-318 ◽  
Author(s):  
E. Gerhards ◽  
M. Rühl
Keyword(s):  
Insulin Secretion ◽  
Chinese Hamster ◽  
Cricetulus Griseus ◽  
Perfused Pancreas ◽  
Short Term ◽  
Isolated Perfused Pancreas ◽  
Perfusion Studies ◽  
Dynamics Of Insulin Secretion ◽  
Linear Manner ◽  
Second Peak

ABSTRACT The insulin secretion pattern of the isolated perfused pancreas of the non-diabetic Chinese hamster after stimulation with glucose and tolbutamide is described. Stimulation with 100–800 mg glucose/100 ml leads to an increasing acute insulin secretion. The initial insulin peak reaches its maximum 2–3 min after the beginning of the stimulation with glucose. The amount of insulin initially secreted from the pancreas of fasted hamsters is larger than that of fed animals. The initial insulin peak is followed by a second short-term insulin release. The maximum of the second peak occurs approximately 10–15 min after the initial stimulation with glucose. With 100 mg glucose/100 ml the insulin secretion proceeds in a practically linear manner for a period of 140 min. With 200 and 400 mg glucose/100 ml the insulin secretion remains linear for approximately 80 min. With 200 mg glucose/100 ml about 10 000 μU insulin are secreted within 120 min, with 400 mg glucose/100 ml approximately 20 000 μU are secreted in the same period of time. The insulin secretion is described following repeated short-term stimulation with 200 mg glucose/100 ml and increasing glucose concentrations up to 500 mg/100 ml for 5 min each. In perfusion studies with 400 mg glucose/100 ml and 8 mg puromycin/100 ml the amount of insulin secreted in 150 min is reduced by about 50%. The insulin secretion stimulated by 100 mg glucose/100 ml was greatly increased by 10 mg tolbutamide/100 ml. The insulin secretion pattern at a glucose concentration of 50 mg/100 ml is shown following repeated stimulation with 10 mg tolbutamide/100 ml alternating with tolbutamide-free resting phases of 10 min. The mechanism of insulin secretion following stimulation with glucose and β-cytotrophic antidiabetics is discussed. The isolated perfused pancreas of the Chinese hamster is suitable for the study of the dynamics of insulin secretion.

Inhibition of Insulin Secretion by Diphenylhydantoin in the Isolated Perfused Pancreas

1970 ◽  
Vol 30 (3) ◽  
pp. 400-401 ◽  
Author(s):  
SEYMOUR R. LEVIN ◽  
JOSEPH BOOKER ◽  
DESMOND F. SMITH ◽  
GEROLD M. GRODSKY
Keyword(s):  
Insulin Secretion ◽  
Perfused Pancreas ◽  
Isolated Perfused Pancreas

scholarly journals Insulin Pulse Characteristics and Insulin Action in Non-Diabetic Humans

2021 ◽  
Author(s):  
Marcello C Laurenti ◽  
Chiara Dalla Man ◽  
Ron T Varghese ◽  
James C Andrews ◽  
John G Jones ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Action ◽  
Univariate Analysis ◽  
Glucose Production ◽  
Pulse Amplitude ◽  
Endogenous Glucose Production ◽  
Deuterated Water ◽  
Endogenous Glucose ◽  
Pulse Characteristics ◽  
Pulsatile Insulin Secretion

Abstract Objective Pulsatile insulin secretion is impaired in diseases such as type 2 diabetes that are characterized by insulin resistance. This has led to the suggestion that changes in insulin pulsatility directly impair insulin signaling. We sought to examine the effects of pulse characteristics on insulin action in humans, hypothesizing that a decrease in pulse amplitude or frequency is associated with impaired hepatic insulin action. Methods We studied 29 nondiabetic subjects on two occasions. On one occasion, hepatic and peripheral insulin action was measured using a euglycemic clamp. The deuterated water method was used to estimate the contribution of gluconeogenesis to endogenous glucose production. On a separate study day we utilized nonparametric stochastic deconvolution of frequently sampled peripheral C-peptide concentrations during fasting to reconstruct portal insulin secretion. In addition to measuring basal and pulsatile insulin secretion, we used Approximate Entropy (ApEn) to measure orderliness and Fourier transform to measure the average, and the dispersion of, insulin pulse frequencies. Results In univariate analysis, basal insulin secretion (R 2 = 0.16) and insulin pulse amplitude (R 2 = 0.09), correlated weakly with insulin-induced suppression of gluconeogenesis. However, after adjustment for age, sex and weight these associations were no longer significant. The other pulse characteristics also did not correlate with the ability of insulin to suppress endogenous glucose production (and gluconeogenesis), or to stimulate glucose disappearance. Conclusions Overall, our data demonstrate that insulin pulse characteristics, considered independently of other factors, do not correlate with measures of hepatic and peripheral insulin sensitivity in non-diabetic humans.

Long-term function of isotransplanted islets of Langerhans in the diabetic rat

1976 ◽  
Vol 54 (6) ◽  
pp. 916-925 ◽  
Author(s):  
E. J. Greenglass ◽  
J. M. Martin
Keyword(s):  
Insulin Secretion ◽  
Diabetic Rats ◽  
Male Rats ◽  
Diabetic Rat ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Experimental Animals ◽  
Functional Development ◽  
Experimental Group

Highly inbred male rats were made diabetic by subtotal pancreatectomy. After diabetes developed, the animals were transplanted with an average of 500 isolated islets, obtained from donors of the same sex and strain, into the portal vein. Groups of islet-transplanted diabetic rats were followed for periods of 3, 6, and 14 months, during which time the performance of the transplanted islets was investigated. Control animals were followed for similar periods of time. The findings obtained from each experimental group were integrated so as to provide a continuous picture of the transplanted islet's behaviour from 2 weeks to 14 months post transplantation.To assess islet performance, normal, untreated diabetic, and transplanted animals were subjected to three stimulatory tests of insulin secretion: (1) oral glucose tolerance, (2) intravenous sulfonylurea, and (3) intraperitoneal L-arginine. Normal and transplanted rats were additionally subjected to one inhibitory test of insulin secretion, diazoxide (given orally). At the end of the study, control and experimental animals were killed, and morphological investigations were performed on liver and pancreas.Isotransplantation of islets in partially depancreatized diabetic rats resulted in the reversal of the condition. The transplanted islets were found to respond to physiologic and pharmacologic controls, although the characteristics of the responses were not identical with that of the normal intact islet. The results of this study have suggested that a functional development of the transplanted islets occurs.

scholarly journals Concordant induction of rapid in vivo pulsatile insulin secretion by recurrent punctuated glucose infusions

2000 ◽  
Vol 278 (1) ◽  
pp. E162-E170 ◽  
Author(s):  
Niels Pørksen ◽  
Claus Juhl ◽  
Malene Hollingdal ◽  
Steve M. Pincus ◽  
Jeppe Sturis ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Release ◽  
Approximate Entropy ◽  
Isolated Perfused Pancreas ◽  
Significance Levels ◽  
Important Regulator ◽  
Glucose Induction ◽  
Frequency Changes ◽  
Pulsatile Insulin Secretion

Insulin is largely secreted as serial secretory bursts superimposed on basal release, insulin secretion is regulated through changes of pulse mass and frequency, and the insulin release pattern affects insulin action. Coordinate insulin release is preserved in the isolated perfused pancreas, suggesting intrapancreatic coordination. However, occurrence of glucose concentration oscillations may influence the process in vivo, as it does for ultradian oscillations. To determine if rapid pulsatile insulin release may be induced by minimal glucose infusions and to define the necessary glucose quantity, we studied six healthy individuals during brief repetitive glucose infusions of 6 and 2 mg ⋅ kg−1⋅ min−1for 1 min every10 min. The higher dose completely synchronized pulsatile insulin release at modest plasma glucose changes (∼0.3 mM = ∼5%), with large (∼100%) amplitude insulin pulses at every single glucose induction ( n = 54) at a lag time of 2 min ( P< 0.05), compared with small (10%) and rare ( n = 3) uninduced insulin excursions. The smaller glucose dose induced insulin pulses at lower significance levels and with considerable breakthrough insulin release. Periodicity shift from either 7- to 12-min or from 12- to 7-min intervals between consecutive glucose (6 mg ⋅ kg−1⋅ min−1) infusions in six volunteers revealed rapid frequency changes. The orderliness of insulin release as estimated by approximate entropy (1.459 ± 0.009 vs. 1.549 ± 0.027, P = 0.016) was significantly improved by glucose pulse induction ( n = 6; 6 mg ⋅ kg−1⋅ min−1) compared with unstimulated insulin profiles ( n = 7). We conclude that rapid in vivo oscillations in glucose may be an important regulator of pulsatile insulin secretion in humans and that the use of an intermittent pulsed glucose induction to evoke defined and recurrent insulin secretory signals may be a useful tool to unveil more subtle defects in β-cell glucose sensitivity.

Somatostatin, glucagon, and insulin secretion from isolated perfused pancreas of new genetically obese hyperglycemic rats

Metabolism ◽  
1984 ◽  
Vol 33 (5) ◽  
pp. 429-431 ◽  
Author(s):  
Yutaka Seino ◽  
Susumu Seino ◽  
Masaru Usami ◽  
Kinsuke Tsuda ◽  
Jiro Takemura ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Perfused Pancreas ◽  
Isolated Perfused Pancreas ◽  
Glucagon And Insulin

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

1996 ◽  
Vol 270 (6) ◽  
pp. E1043-E1049 ◽  
Author(s):  
N. Porksen ◽  
S. R. Munn ◽  
J. L. Steers ◽  
J. D. Veldhuis ◽  
P. C. Butler
Keyword(s):  
Insulin Secretion ◽  
Pulse Amplitude ◽  
Selective Inhibition ◽  
Canine Model ◽  
Pulse Frequency ◽  
Insulin Clearance ◽  
Glucose Ingestion ◽  
Total Body ◽  
Pulsatile Insulin Secretion ◽  
Body Clearance

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.

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