Impaired phosphoinositide metabolism in glucose-incompetent islets of neonatally streptozotocin-diabetic rats

1997 ◽  
Vol 272 (5) ◽  
pp. E737-E745 ◽  
Author(s):  
L. Morin ◽  
M. H. Giroix ◽  
M. N. Gangnerau ◽  
D. Bailbe ◽  
B. Portha
Keyword(s):  
Insulin Secretion ◽  
Inositol Phosphates ◽  
Insulin Dependent Diabetes Mellitus ◽  
Diabetic Rats ◽  
Dependent Diabetes Mellitus ◽  
Phosphoinositide Metabolism ◽  
Pi Turnover ◽  
Insulin Dependent ◽  
Glucose Stimulated Insulin Secretion ◽  
Phosphatidylinositol 4

The effects of nutrient and neurotransmitter stimuli on insulin release, loss of phosphoinositides (PI), and production of inositol phosphates (InsP) were investigated in islets from neonatally streptozotocin-injected (nSTZ) rats. In islets from nSTZ rats, insulin secretory responses to 16.7 mM D-glucose and 10.0 mM D-glyceraldehyde were reduced compared with controls. Contents in phosphatidylinositol 4-monophosphate [PtdIns(4)P] and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2], but not in phosphatidylinositol, were diminished. Glucose effects on breakdown of PtdIns(4)P and PtdIns(4,5)P2 and on total InsP accumulation were both reduced. D-Glucose was unable to increase the levels of both inositol trisphosphate isomers, Ins(1,3,4)P3 and Ins(1,4,5)P3. Glyceraldehyde also failed to promote InsP formation. By contrast, the ability of 1.0 mM carbachol or 300 nM cholecystokinin to stimulate insulin secretion and InsP generation was still observed. Thus a disturbed coupling between nutrient recognition and activation of phospholipase C, possibly together with a shortage of available polyphosphoinositides, could be responsible for the altered islet PI turnover in the nSTZ rats. It is proposed that such defects may contribute to the impairment of glucose-stimulated insulin secretion in this model of non-insulin-dependent diabetes mellitus.

scholarly journals Role of ATP and Pi in the mechanism of insulin secretion in the mouse insulinoma βTC3 cell line

1997 ◽  
Vol 326 (3) ◽  
pp. 807-814 ◽  
Author(s):  
Klearchos K. PAPAS ◽  
Robert C. LONG ◽  
Ioannis CONSTANTINIDIS ◽  
Athanassios SAMBANIS
Keyword(s):  
Insulin Secretion ◽  
Glucose Concentration ◽  
Insulin Dependent Diabetes Mellitus ◽  
Term Treatment ◽  
Dependent Diabetes Mellitus ◽  
Bioartificial Pancreas ◽  
Long Term Treatment ◽  
Insulin Dependent ◽  
Glucose Stimulated Insulin Secretion

Understanding the biochemical events associated with glucose-stimulated insulin secretion by pancreatic β cells is of importance in gaining insight into both the pathophysiology of diabetes and the development of tissue-engineered bioartificial pancreatic substitutes. We have investigated the effects of glucose concentration on the bioenergetic status and on the metabolic and secretory functions exhibited by mouse insulinoma βTC3 cells entrapped in calcium alginate/poly-L-lysine/alginate (APA) beads. Cells entrapped in APA beads constitute a possible implantable bioartificial pancreas for the long-term treatment of insulin-dependent diabetes mellitus. Our results show that, in entrapped βTC3 cells, the oxygen consumption rate and the intracellular nucleotide triphosphate levels are unaffected by a step change in glucose concentration from 16 mM to 0 mM for 4.5 h and then back to 16 mM. The intracellular Pi level and the ammonia production rate were doubled, while insulin secretion was decreased 10-fold, upon switching from 16 mM to 0 mM glucose. The implications of these findings in the context of pancreatic β cell biochemistry and the mechanism of the ‘Fuel Hypothesis’ are discussed.

ATP-Regulated K+ Channels and Diabetes Mellitus

Physiology ◽  
1990 ◽  
Vol 5 (4) ◽  
pp. 143-147 ◽  
Author(s):  
P Rorsman ◽  
P-O Berggren ◽  
K Bokvist ◽  
S Efendic
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Secretion ◽  
Pancreatic Beta Cells ◽  
Insulin Dependent Diabetes Mellitus ◽  
Dependent Diabetes Mellitus ◽  
K Channel ◽  
K Channels ◽  
Channel Regulation ◽  
Insulin Dependent ◽  
Glucose Stimulated Insulin Secretion

Glucose-stimulated insulin secretion from pancreatic Beta-cells is dependent on closure of ATP-regulated K+ channels. These channels are selectively blocked by hypoglycaemic sulfonylureas, compounds used in treatment of non-insulin-dependent diabetes mellitus (NIDDM). This suggests that NIDDM may result from defective K+-channel regulation.

SAM prevents impairment of glucose-stimulated insulin secretion caused by hexose deprivation or starvation

1995 ◽  
Vol 268 (4) ◽  
pp. E580-E587
Author(s):  
I. Conget ◽  
T. M. Zhang ◽  
D. L. Eizirik ◽  
W. J. Malaisse
Keyword(s):  
B Cell ◽  
Culture Medium ◽  
Glucose Deprivation ◽  
Insulin Dependent Diabetes Mellitus ◽  
Secretory Response ◽  
Dependent Diabetes Mellitus ◽  
Secretory Potential ◽  
Insulin Dependent ◽  
Low Glucose ◽  
Glucose Stimulated Insulin Secretion

Succinic acid monomethyl ester (SAM) was recently proposed as an insulinotropic tool in non-insulin-dependent diabetes mellitus. Three models were now used to investigate whether SAM protects the B-cell against the impairment of glucose-stimulated insulin release caused by either glucose deprivation or starvation. In the first model, preincubation of the islets for 180 min at low glucose concentration in the presence of SAM prevented the decrease in the secretory response to D-glucose otherwise observed during a subsequent incubation. In the second model, an impaired secretory response to D-glucose was observed after 3-day culture at low (2.8 or 5.6 mM) as distinct from high (11.1 mM) hexose concentration and the presence of SAM in the culture medium again protected against this anomaly. In the third model, the infusion of SAM for 3 days to starved rats restored the secretory potential of isolated islets to a level comparable to that otherwise found in fed rats. Thus, during glucose deprivation or starvation, SAM is indeed able to maintain B-cell responsiveness to D-glucose.

scholarly journals Induction and maintenance of remission of insulin-dependent diabetes mellitus in repeated courses of hyperbaric oxygenation

1999 ◽  
Vol 45 (4) ◽  
pp. 10-13
Author(s):  
A. V. Dreval ◽  
V. A. Gubkina ◽  
S. O. Kiselev ◽  
R. S. Tishenin ◽  
G. S. Molchanov ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Secretion ◽  
Hyperbaric Oxygenation ◽  
Insulin Dependent Diabetes Mellitus ◽  
Diabetes Remission ◽  
Diabetes Duration ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Patients With Diabetes ◽  
Insulin Dependent

The efficacy of hyperbaric oxygenation (HBO) is studied in diabetics with newly detected or lasting for less than 1 year disease. The possibility of inducing and/or prolonging diabetes remission by HBO and the efficacy of repeated courses of HBO are evaluated. Fifty-three patients with insulin-dependent diabetes mellitus (IDDM) (28 men and 25 women) aged 15-39 years, suffering from the disease for up to 12 month without apparent complications, were administered intensive insulin therapy with human insulin preparations and 10-day HBO courses. HBO courses repeated every 4 months promoted compensation of carbohydrate metabolism by stimulating residual insulin secretion in patients with IDDM lasting for up to one year, the effect of HBO progressively decreasing with each course. Manifest positive effect of HBO persisted for 2 months. After the first course of HBO, remission of IDDM ensued in 41.5% cases. Patients aged over 25 years with intact insulin secretion on an empty stomach were more disposed to remission. Remissions were equally incident in patients with diabetes duration of up to 6 months and in those with diabetes duration of 6-12 months. A history of ketoacidotic coma episodes does not rule out the induction of a remission.

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