Table 1.

Alterations in the adrenal gland in response to recurrent glucoprivation/hypoglycaemia in diabetic and non-diabetic rodents. 2DG, 2-deoxy glucose, ASNA, adrenal sympathetic nerve activity; Ad, adrenaline; NAd, noradrenaline; AChR, acetylcholine receptor; ERK, extracellular signal regulated protein kinase; PKA, protein kinase A; PKC, protein kinase C; TH, tyrosine hydroxylase; DBH, dopamine β-hydroxylase; RH, single daily recurrent hypoglycaemia; 2RH, twice daily episodes of insulin-induced hypoglycaemia; PNMT, phenylethanolamine N-methyltransferase.

Alterations in the Adrenal Gland	Species	Recurrent 2DG/Insulin, Dose, and Route of Administration	Number of Antecedent Episodes	Finding in Response to Subsequent Glucoprivation/Hypoglycaemia	Time of Measurement	Plasma Adrenaline in Response to Single/Recurrent Hypoglycaemia
Catecholamine release	Non-diabetic mice	Insulin, 2.5 U/kg; i.p. [89]	Once a day for 5 days [89]	↓ adrenaline response [89]	30 min from the last injection [89]	~16/7 ng/mL [89]
	Non-diabetic rats	Insulin, 2 U/kg; i.p. [37]	Twice a day for 3 days [37]	↓ expression of genes of proteins associated with exocytosis [37]	60 min from the last injection [37]	Did not measure [37]
		Insulin, 5 U/kg; i.p. [88]	Once a day for 3 days [88]	↓ adrenaline response [88]	2 h from the last injection [88]	1317/170.7 pg/mL [88]
	Diabetic rats	Insulin, 30–40 IU/kg; i.p. [87]	Once a day for 3 days [87]	↓ adrenaline response [87]	90 min from the last injection [87]	5000/2500 pg/mL [87]
		Insulin, 5 U/kg; i.p. [88]	Once a day for 3 days [88]	↔ adrenaline response [88]	2 h from the last injection [88]	2958/3804 pg/mL [88]
Adrenal sympathetic nerve activity/ stimulation	Non-diabetic rats	Insulin, 1.5 U/kg; s.c. [36]	Once a day for 2 days [36]	↔ASNA [36]	During the subsequent hypoglycaemic episode [36]	~2800/1200 pg/mL [36]
		Insulin, 2 U/kg; s.c. [31]	Once a day for 2 days [31]	↔ASNA [31]	During the subsequent hypotensive episode [31]	~1100/700 pg/mL [31]
		Insulin, 1 U/kg; s.c. [35]	Once a day for 3 days [35]	a. ↓ Ad and NAd release in response to nerve stimulation; b. ↔ Ad and NAd release in response to AChR agonists [35]	a. Day 4; b. Day 5 [35]	707 ± 89/458 ± 135 pg/mL [35]
Chromaffin cell activation	Non-diabetic rats	2DG, 200 mg/kg; s.c. [76]	Once a day for 10 days [76]	Reduced Fos expression [76]	2 h from the last injection [76]	Did not measure [76]
Intracellular signalling	Non-diabetic rats	Insulin, 10 U/kg; i.p. [98]	Once a day for 2 days [98]	↔ ERK 1/2 activation [98]	60 min from the last injection [98]	4417 ± 594/2617 ± 185 pg/mL [98]
		Insulin, 2 U/kg; i.p. [32]	Once a day (RH) and twice a day (2RH) for 3 days [32]	↔ PKA activation [32]	60 min from the last injection [32]	~2/2 ng/mL (RH) ~2.8/1.5 ng/mL (2RH) [32]
		Insulin, 2 U/kg; i.p. [37]	Twice a day for 3 days [37]	↓ PKC gene expression [37]	60 min from the last injection [37]	Did not measure [37]
Adrenal gland catecholamine content	Non-diabetic rats	Insulin, 2 U/kg; s.c. [31]	Once a day for 2 days [31]	↓ Adrenaline content of the adrenal gland [31]	Measured on the day after the second hypoglycaemic episode [31]	~1100/700 pg/mL [31]
		Insulin, 1 U/kg; s.c. [35]	Once a day for 3 days [35]	↔ Adrenaline content of the adrenal gland [35]	Measured on the day after the subsequent hypoglycaemic episode [35]	707 ± 89/458 ± 135 pg/mL [35]
TH mRNA, protein, and phosphorylation	Non-diabetic rats [31,32,79,98,110,112]	2DG, 500 mg/kg and Insulin, 5 U/kg; i.p. [79]	Once a day for 6 days [79]	↑ TH mRNA [79] [110]	5 h after the seventh injection [79]	Did not measure [79]
		2DG, 500 mg/kg and Insulin, 5 U/kg; i.p. [110]	Once a day for 5 and 6 days [110]	↑ TH mRNA ↑ TH protein [110]	24 h after the sixth injection and 5 h after the seventh injection [110]	Did not measure [110]
		Insulin, 2 U/kg; i.p. [32]	Once a day (RH) and twice a day (2RH) for 3 days [32]	↓ TH mRNA (2RH) ↓ Ser40TH phosphorylation ↑ TH protein (2RH) [32]	TH mRNA: 3.5 h from the end of hypoglycaemic clamp on the last day; TH protein and pSer40TH at 60 min from the last injection [32]	~2/2 ng/mL (RH) ~2.8/1.5 ng/mL (2RH) [32]
		2DG, 500 mg/kg and Insulin, 2 U/kg; s.c. [112]	Once a day for 5 days [112]	↑ TH protein [112]	6 h after the administration of the last dose of 2DG/insulin [112]	Did not measure [112]
		Insulin, 10 U/kg; i.p. [98]	Once a day for 2 days [98]	↑ TH protein ↑ Ser40TH phosphorylation [98]	60 min from the subsequent episode [98]	4417 ± 594/2617 ± 185 pg/mL [98]
		Insulin, 2 U/kg; s.c. [31]	Once a day for 2 days [31]	↔ TH protein ↔ Ser40TH phosphorylation [31]	Day after the second hypoglycaemic episode [31]	~1100/700 pg/mL [31]
	Non-diabetic mice [34]	Insulin, 2.5 U/kg; i.p. [34]	Once a day for 3 days [34]	↓ TH immunoreactivity [20,34]	24 h after the last injection [34]	~7/4 ng/mL [34]
	Untreated diabetic rats [111]	Insulin, 2 U/kg; s.c. [111]	Twice a day for 4 days [111]	↔ TH mRNA [111]	Not given [111]	Did not measure [111]
	Insulin-treated diabetic rats [113]	Insulin, 2 U/kg; s.c. [113]	Twice a day for 3 days and one episode on day 4 [113]	↔ TH mRNA ↑ TH protein [113]	At 90 min during the subsequent episode [113]	~30/25 nM [113]
DBH Protein expression	Non-diabetic rats [98,112]	Insulin, 10 U/kg; i.p. [98]	Once a day for 2 days [98]	↔ DBH protein [98]	60 min from the subsequent episode [98]	4417 ± 594/2617 ± 185 pg/mL [98]
		2DG, 500 mg/kg and Insulin, 2 U/kg; s.c. [112]	Once a day for 5 days [112]	↑ DBH protein [112]	6 h after the administration of the last dose of 2DG/insulin [112]	Did not measure [112]
	Untreated diabetic rats [111]	2DG, 500 mg/kg and Insulin, 2 U/kg; s.c. [111]	Twice a day for 4 days [111]	↑ DBH mRNA [111]	Not given [111]	Did not measure [111]
	Insulin-treated diabetic rats [113]	2DG, 500 mg/kg and Insulin, 2 U/kg; s.c. [113]	Twice a day for 3 days and one episode on day 4 [113]	↓ DBH protein [113]	At 90 min during the subsequent episode [113]	~30/25 nM [113]
PNMT mRNA and protein expression	Non-diabetic rats [31,32,98,112]	Insulin, 2 U/kg; s.c. [31]	Once a day for 2 days [31,98]	↔ PNMT protein [31]	Day after the second hypoglycaemic episode [31]	~1100/700 pg/mL [31]
		Insulin, 2 U/kg; i.p. [32]	Once a day (RH) and twice a day (2RH) for 3 days [32]	↔ PNMT mRNA [32]	3.5 h from the end of hypoglycaemic clamp on the last day [32]	~2/2 ng/mL (RH) ~2.8/1.5 ng/mL (2RH) [32]
		Insulin, 10 U/kg; i.p. [98]	Once a day for 2 days [98]	↔ PNMT protein [98]	60 min from the subsequent episode [98]	4417 ± 594/2617 ± 185 pg/mL [98]
		2DG, 500 mg/kg and Insulin, 2 U/kg; s.c. [112]	Once a day for 5 days [112]	↑ PNMT protein (insulin) ↔ PNMT protein (2DG) [112]	6 h after the administration of the last dose of 2DG/insulin [112]	Did not measure [112]
	Untreated diabetic rats [111]	2DG, 500 mg/kg and Insulin, 2 U/kg; s.c. [111]	Twice a day for 4 days [111]	↓ PNMT mRNA [111]	Not given [111]	Did not measure [111]
	Insulin-treated diabetic rats [113]	2DG, 500 mg/kg and Insulin, 2 U/kg; s.c. [113]	Twice a day for 3 days and one episode on day 4 [113]	↔ PNMT mRNA and PNMT protein [113]	At 90 min during the subsequent episode [113]	~30/25 nM [113]

↓ indicates a decrease; ↑ indicates an increase; ↔, indicates no change.